2,440 results match your criteria DNA Repair [Journal]


Deployment of DNA polymerases beta and lambda in single-nucleotide and multinucleotide pathways of mammalian base excision DNA repair.

DNA Repair (Amst) 2019 Feb 4;76:11-19. Epub 2019 Feb 4.

Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY 11794, United States; Department of Pharmacological Sciences, Stony Brook University School of Medicine, Stony Brook, NY, 11794, United States. Electronic address:

There exist two major base excision DNA repair (BER) pathways, namely single-nucleotide or "short-patch" (SP-BER), and "long-patch" BER (LP-BER). Both pathways appear to be involved in the repair of small base lesions such as uracil, abasic sites and oxidized bases. In addition to DNA polymerase β (Polβ) as the main BER enzyme for repair synthesis, there is evidence for a minor role for DNA polymerase lambda (Polλ) in BER. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.001DOI Listing
February 2019

The MCM8/9 complex: A recent recruit to the roster of helicases involved in genome maintenance.

DNA Repair (Amst) 2019 Feb 5;76:1-10. Epub 2019 Feb 5.

Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, 76798, USA. Electronic address:

There are several DNA helicases involved in seemingly overlapping aspects of homologous and homoeologous recombination. Mutations of many of these helicases are directly implicated in genetic diseases including cancer, rapid aging, and infertility. MCM8/9 are recent additions to the catalog of helicases involved in recombination, and so far, the evidence is sparse, making assignment of function difficult. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183031
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http://dx.doi.org/10.1016/j.dnarep.2019.02.003DOI Listing
February 2019
1 Read

Identification and quantification of DNA repair protein poly(ADP ribose) polymerase 1 (PARP1) in human tissues and cultured cells by liquid chromatography/isotope-dilution tandem mass spectrometry.

DNA Repair (Amst) 2019 Feb 1;75:48-59. Epub 2019 Feb 1.

Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, United States. Electronic address:

Poly(ADP ribose) polymerase 1 (PARP1) is a multifunctional DNA repair protein of the base excision repair pathway and plays a major role in the repair of DNA strand breaks and in replication and transcriptional regulation among other functions. Mounting evidence points to the predictive and prognostic value of PARP1 expression in human cancers. Thus, PARP1 has become an important target in cancer therapy, leading to the development of inhibitors as anticancer drugs. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.01.008DOI Listing
February 2019

Azoospermic infertility is associated with altered expression of DNA repair genes.

DNA Repair (Amst) 2019 Jan 24;75:39-47. Epub 2019 Jan 24.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India. Electronic address:

Compelling evidence suggest that germs cells are predominantly sensitive to DNA damaging agents in comparison to other cells. High fidelity DNA repair in testicular cells thus becomes indispensable to preserve the genomic integrity for passing on to the progeny. Compromised DNA repair machinery in the testicular cells may result in impaired spermatogenesis and infertility. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183024
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http://dx.doi.org/10.1016/j.dnarep.2019.01.006DOI Listing
January 2019
4 Reads

Biochemical characterization of mismatch-binding protein MutS1 and nicking endonuclease MutL from a euryarchaeon Methanosaeta thermophila.

DNA Repair (Amst) 2019 Jan 25;75:29-38. Epub 2019 Jan 25.

Agricultural Science, Graduate School of Integrated Arts and Sciences, Kochi University, 200 Otsu, Monobe, Nankoku, Kochi, 783-8502, Japan. Electronic address:

In eukaryotes and most bacteria, the MutS1/MutL-dependent mismatch repair system (MMR) corrects DNA mismatches that arise as replication errors. MutS1 recognizes mismatched DNA and stimulates the nicking endonuclease activity of MutL to incise mismatch-containing DNA. In archaea, there has been no experimental evidence to support the existence of the MutS1/MutL-dependent MMR. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.01.005DOI Listing
January 2019

Single-strand annealing mediates the conservative repair of double-strand DNA breaks in homologous recombination-defective germ cells of Caenorhabditis elegans.

DNA Repair (Amst) 2019 Jan 24;75:18-28. Epub 2019 Jan 24.

Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, 03772, Seoul, Republic of Korea. Electronic address:

A missense mutation in C. elegans RAD-54, a homolog of RAD54 that operates in the homologous recombination (HR) pathway, was found to decrease ATPase activity in vitro. The hypomorphic mutation caused hypersensitivity of C. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.01.007DOI Listing
January 2019

Sources of thymidine and analogs fueling futile damage-repair cycles and ss-gap accumulation during thymine starvation in Escherichia coli.

DNA Repair (Amst) 2019 Jan 16;75:1-17. Epub 2019 Jan 16.

Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. Electronic address:

Thymine deprivation in thyA mutant E. coli causes thymineless death (TLD) and is the mode of action of popular antibacterial and anticancer drugs, yet the mechanisms of TLD are still unclear. TLD comprises three defined phases: resistance, rapid exponential death (RED) and survival, with the nature of the resistance phase and of the transition to the RED phase holding key to TLD pathology. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.01.002DOI Listing
January 2019
1 Read

An open-source algorithm for rapid unbiased determination of DNA fiber length.

DNA Repair (Amst) 2019 Feb 11;74:26-37. Epub 2019 Jan 11.

Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada; Département d'Ophtalmologie, Université de Montréal, Montréal, Québec, Canada. Electronic address:

DNA fiber fluorography is widely employed to study the kinetics of DNA replication, but the usefulness of this approach has been limited by the lack of freely-available automated analysis tools. Quantification of DNA fibers usually relies on manual examination of immunofluorescence microscopy images, which is laborious and prone to inter- and intra-operator variability. To address this, we developed an unbiased, fully automated algorithm that quantifies length and color of DNA fibers from fluorescence microscopy images. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.01.003DOI Listing
February 2019

Mechanistic insights into the enzymatic activity and inhibition of the replicative polymerase exonuclease domain from Mycobacterium tuberculosis.

DNA Repair (Amst) 2019 Feb 26;74:17-25. Epub 2018 Dec 26.

Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, 97080 Würzburg, Germany.

DNA replication fidelity maintains low mutation rates in bacteria. The ε-subunit of a replisome generally acts as the main proofreader during replication, using its 3'-5' exonuclease activity to excise misincorporated bases thereby maintaining faithful replication. In Mycobacterium tuberculosis (Mtb), however, the polymerase and histidinol phosphatase (PHP) domain of the DNA polymerase DnaE1 is the primary proofreader. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.12.006DOI Listing
February 2019
1 Read

Budding yeast Rtt107 prevents checkpoint hyperactivation after replicative stress by limiting DNA damage.

DNA Repair (Amst) 2019 Feb 6;74:1-16. Epub 2019 Jan 6.

Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. Electronic address:

Cells respond to DNA damage by activating cell cycle checkpoints, arresting cell division or DNA replication while damage is repaired. In Saccharomyces cerevisiae, activation of the checkpoint kinase Rad53 leads to cell cycle arrest, with Rad53 deactivation required for proper resumption of the cell cycle. Rtt107 is a S. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.01.001DOI Listing
February 2019
1 Read

Spy1, a unique cell cycle regulator, alters viability in ALS motor neurons and cell lines in response to mutant SOD1-induced DNA damage.

DNA Repair (Amst) 2019 Feb 21;74:51-62. Epub 2018 Dec 21.

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China. Electronic address:

Increasing evidence indicates that DNA damage and p53 activation play major roles in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). Human SpeedyA1 (Spy1), a member of the Speedy/Ringo family, enhances cell proliferation and promotes tumorigenesis. Further studies have demonstrated that Spy1 promotes cell survival and inhibits DNA damage-induced apoptosis. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.12.005DOI Listing
February 2019
8 Reads

Mammalian INO80 chromatin remodeler cooperates with FANCM to mediate DNA interstrand crosslink-induced checkpoint activation and repair.

DNA Repair (Amst) 2019 Feb 30;74:38-50. Epub 2018 Dec 30.

Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 21, 1113 Sofia, Bulgaria. Electronic address:

Chromatin regulators play crucial roles in the DNA damage response. While the chromatin changes needed for double-strand break repair and nucleotide excision repair have been intensely studied, the chromatin requirements of interstrand crosslink (ICL) repair have remained largely unexplored. Here, we studied the effect of silencing the INO80 chromatin remodeler subunits on the cellular response to ICLs. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.12.007DOI Listing
February 2019
2 Reads

Double-strand break repair plays a role in repeat instability in a fragile X mouse model.

DNA Repair (Amst) 2019 Feb 21;74:63-69. Epub 2018 Dec 21.

Section on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, United States. Electronic address:

Expansion of a CGG-repeat tract in the 5' UTR of FMR1 is responsible for the Fragile X-related disorders (FXDs), FXTAS, FXPOI and FXS. Previous work in a mouse model of these disorders has implicated proteins in the base excision and the mismatch repair (MMR) pathways in the expansion mechanism. However, the precise role of these factors in this process is not well understood. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183029
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http://dx.doi.org/10.1016/j.dnarep.2018.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366319PMC
February 2019
13 Reads

Cancer risk from low dose radiation in Ptch1 mice with inactive DNA repair systems: Therapeutic implications for medulloblastoma.

DNA Repair (Amst) 2019 Feb 16;74:70-79. Epub 2018 Dec 16.

Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy. Electronic address:

DSBs are harmful lesions produced through endogenous metabolism or by exogenous agents such as ionizing radiation, that can trigger genomic rearrangements. We have recently shown that exposure to 2 Gy of X-rays has opposite effects on the induction of Shh-dependent MB in NHEJ- and HR-deficient Ptch1 mice. In the current study we provide a comprehensive link on the role of HR/NHEJ at low doses (0. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.12.003DOI Listing
February 2019
3 Reads

Repair of protein-linked DNA double strand breaks: Using the adenovirus genome as a model substrate in cell-based assays.

DNA Repair (Amst) 2019 Feb 10;74:80-90. Epub 2018 Dec 10.

Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, 92037, USA. Electronic address:

The DNA double strand breaks (DSBs) created during meiotic recombination and during some types of chemotherapy contain protein covalently attached to their 5' termini. Removal of the end-blocking protein is a prerequisite to DSB processing by non-homologous end-joining or homologous recombination. One mechanism for removing the protein involves CtIP-stimulated Mre11-catalyzed nicking of the protein-linked strand distal to the DSB terminus, releasing the end-blocking protein while it remains covalently attached to an oligonucleotide. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.12.001DOI Listing
February 2019
1 Read

SetR a negative transcriptional regulator of the integrating conjugative element 391 mutagenic response.

DNA Repair (Amst) 2019 Jan 16;73:99-109. Epub 2018 Nov 16.

Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA.

The integrating conjugative element ICE391 (formerly known as IncJ R391) harbors an error-prone DNA polymerase V ortholog, polV, encoded by the ICE391 rumAB operon. polV and its orthologs have previously been shown to be major contributors to spontaneous and DNA damage-induced mutagenesis in vivo. As a result, multiple levels of regulation are imposed on the polymerases so as to avoid aberrant mutagenesis. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.007DOI Listing
January 2019
1 Read

Synthetic lethality between DNA repair factors Xlf and Paxx is rescued by inactivation of Trp53.

DNA Repair (Amst) 2019 Jan 16;73:164-169. Epub 2018 Dec 16.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Laboratory Center, Erling Skjalgssons gate 1, 7491, Trondheim, Norway; St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250 Sluppen, 7006, Trondheim, Norway; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. Electronic address:

Non-homologous end joining (NHEJ) is a DNA repair pathway that senses, processes and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. During NHEJ, core Ku70 and Ku80 subunits bind DSBs as a heterodimer and promote further recruitment of accessory factors (e.g. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.12.002DOI Listing
January 2019
1 Read

Rotational and translational positions determine the structural and dynamic impact of a single ribonucleotide incorporated in the nucleosome.

DNA Repair (Amst) 2019 Jan 29;73:155-163. Epub 2018 Nov 29.

Department of Biology, New York University, 100 Washington Square East, New York, NY, 10003, United States. Electronic address:

Ribonucleotides misincorporated by replicative DNA polymerases are by far the most common DNA lesion. The presence of ribonucleotides in DNA is associated with genome instability, causing replication stress, chromosome fragility, gross chromosomal rearrangements, and other mutagenic events. Furthermore, nucleosome and chromatin assembly as well as nucleosome positioning are affected by the presence of ribonucleotides. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.012DOI Listing
January 2019
1 Read

The absence of the RecN protein suppresses the cellular defects of Deinococcus radiodurans irradiated cells devoid of the PprA protein by limiting recombinational repair of DNA lesions.

DNA Repair (Amst) 2019 Jan 28;73:144-154. Epub 2018 Nov 28.

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France. Electronic address:

The Deinococcus radiodurans bacterium is one of the most radioresistant organisms known. It can repair hundreds of radiation-induced DNA double-strand breaks without loss of viability and reconstitute an intact genome through RecA-dependent and RecA-independent DNA repair pathways. Among the Deinococcus specific proteins required for radioresistance, the PprA protein was shown to play a major role for accurate chromosome segregation and cell division after completion of DNA repair. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.011DOI Listing
January 2019
2 Reads

Correcting errors in the BRCA1 warning system.

DNA Repair (Amst) 2019 Jan 22;73:120-128. Epub 2018 Nov 22.

Virgina Tech Carilion Research Institute, Virginia Tech, Roanoke, Virginia, 24016, USA; Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, 16802, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA; Center for Structural Oncology, Pennsylvania State University, University Park, PA, 16802, USA. Electronic address:

Given its important role in human health and disease, remarkably little is known about the full-length three-dimensional (3D) molecular architecture of the breast cancer type 1 susceptibility protein (BRCA1), or its mechanisms to engage the tumor suppressor, TP53 (p53). Here, we show how a prevalent cancer-related mutation in the C-terminal region of the full-length protein, BRCA1, affects its structural properties, yet can be biochemically corrected to restore its functional capacity. As a downstream consequence of restoring the ubiquitin ligase activity of mutated BRCA1, the DNA repair response of p53 was enhanced in cellular extracts naturally deficient in BRCA1 protein expression. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.009DOI Listing
January 2019
1 Read

Proteasome inhibition prevents cell death induced by the chemotherapeutic agent cisplatin downstream of DNA damage.

DNA Repair (Amst) 2019 Jan 25;73:28-33. Epub 2018 Oct 25.

Centro de Biologia Molecular e Ambiental, Departamento de Biologia, Universidade do Minho, Braga, Portugal. Electronic address:

Cisplatin is a highly effective chemotherapeutic drug acting as a DNA-damaging agent that induces apoptosis of rapidly proliferating cells. Unfortunately, cellular resistance still occurs. Mutations in p53 in a large fraction of tumor cells contribute to defects in apoptotic pathways and drug resistance. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183002
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http://dx.doi.org/10.1016/j.dnarep.2018.10.006DOI Listing
January 2019
5 Reads

Human AP-endonuclease (Ape1) activity on telomeric G4 structures is modulated by acetylatable lysine residues in the N-terminal sequence.

DNA Repair (Amst) 2019 Jan 22;73:129-143. Epub 2018 Nov 22.

Laboratory of Molecular Biology and DNA Repair, Department of Medicine (DAME), University of Udine, Udine, Italy. Electronic address:

Loss of telomeres stability is a hallmark of cancer cells. Exposed telomeres are prone to aberrant end-joining reactions leading to chromosomal fusions and translocations. Human telomeres contain repeated TTAGGG elements, in which the 3' exposed strand may adopt a G-quadruplex (G4) structure. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183024
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http://dx.doi.org/10.1016/j.dnarep.2018.11.010DOI Listing
January 2019
2 Reads

53BP1: A key player of DNA damage response with critical functions in cancer.

DNA Repair (Amst) 2019 Jan 20;73:110-119. Epub 2018 Nov 20.

Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

Maintenance of genome integrity and stability is a critical responsibility of the DNA damage response (DDR) within cells, such that any disruption in this kinase-based signaling pathway leads to development of various disorders, particularly cancer. The tumor suppressor P53-binding protein 1 (53BP1), as one of the main mediators of DDR, plays a pivotal role in orchestrating the choice of double-strand break (DSB) repair pathway and contains interaction surfaces for numerous DSB-responsive proteins. It has been extensively demonstrated that aberrant expression of 53BP1 contributes to tumor occurrence and development. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183026
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http://dx.doi.org/10.1016/j.dnarep.2018.11.008DOI Listing
January 2019
87 Reads

NuA4 acetyltransferase is required for efficient nucleotide excision repair in yeast.

DNA Repair (Amst) 2019 Jan 14;73:91-98. Epub 2018 Nov 14.

School of Molecular Biosciences, Washington State University, Pullman, WA, 99164, United States; Center for Reproductive Biology, Washington State University, Pullman, WA, 99164, United States. Electronic address:

The nucleotide excision repair (NER) pathway is critical for removing damage induced by ultraviolet (UV) light and other helix-distorting lesions from cellular DNA. While efficient NER is critical to avoid cell death and mutagenesis, NER activity is inhibited in chromatin due to the association of lesion-containing DNA with histone proteins. Histone acetylation has emerged as an important mechanism for facilitating NER in chromatin, particularly acetylation catalyzed by the Spt-Ada-Gcn5 acetyltransferase (SAGA); however, it is not known if other histone acetyltransferases (HATs) promote NER activity in chromatin. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183016
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http://dx.doi.org/10.1016/j.dnarep.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312484PMC
January 2019
10 Reads

The DNA damage response is developmentally regulated in the African trypanosome.

DNA Repair (Amst) 2019 Jan 14;73:78-90. Epub 2018 Nov 14.

The Wellcome Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, UK. Electronic address:

Genomes are affected by a wide range of damage, which has resulted in the evolution of a number of widely conserved DNA repair pathways. Most of these repair reactions have been described in the African trypanosome Trypanosoma brucei, which is a genetically tractable eukaryotic microbe and important human and animal parasite, but little work has considered how the DNA damage response operates throughout the T. brucei life cycle. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329875PMC
January 2019
1 Read

Loss of the p12 subunit of DNA polymerase delta leads to a defect in HR and sensitization to PARP inhibitors.

DNA Repair (Amst) 2019 Jan 13;73:64-70. Epub 2018 Nov 13.

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, United States. Electronic address:

Human DNA polymerase δ is normally present in unstressed, non-dividing cells as a heterotetramer (Pol δ4). Its smallest subunit, p12, is transiently degraded in response to UV damage, as well as during the entry into S-phase, resulting in the conversion of Pol δ4 to a trimer (Pol δ3). In order to further understand the specific cellular roles of these two forms of Pol δ, the gene (POLD4) encoding p12 was disrupted by CRISPR/Cas9 to produce p12 knockout (p12KO) cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312503PMC
January 2019
7 Reads

The Ataxia telangiectasia-mutated and Rad3-related protein kinase regulates cellular hydrogen sulfide concentrations.

DNA Repair (Amst) 2019 Jan 13;73:55-63. Epub 2018 Nov 13.

Department of Pathology & Translational Pathobiology, LSU Health Sciences Center Shreveport, Shreveport, Louisiana, 71130, United States. Electronic address:

The ataxia telangiectasia-mutated and Rad3-related (ATR) serine/threonine kinase plays a central role in the repair of replication-associated DNA damage, the maintenance of S and G2/M-phase genomic stability, and the promotion of faithful mitotic chromosomal segregation. A number of stimuli activate ATR, including persistent single-stranded DNA at stalled replication folks, R loop formation, hypoxia, ultraviolet light, and oxidative stress, leading to ATR-mediated protein phosphorylation. Recently, hydrogen sulfide (HS), an endogenous gasotransmitter, has been found to regulate multiple cellular processes through complex redox reactions under similar cell stress environments. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.002DOI Listing
January 2019
9 Reads

Repair pathway for PARP-1 DNA-protein crosslinks.

DNA Repair (Amst) 2019 Jan 12;73:71-77. Epub 2018 Nov 12.

Genome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA. Electronic address:

Poly(ADP-ribose) polymerase-1 (PARP-1) is a regulatory enzyme involved in many different processes of DNA and RNA metabolism, including DNA repair. Previously, PARP-1 was found capable of forming a covalent DNA-protein crosslink (DPC) at the apurinic/apyrimidinic (AP) site in double-stranded DNA. The C1´ atom of the AP site participates in Schiff base formation with a lysine side chain in PARP-1, and a covalent bond is formed upon reduction of the Schiff base. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312470PMC
January 2019
11 Reads

Architects meets Repairers: The interplay between homeobox genes and DNA repair.

DNA Repair (Amst) 2019 Jan 1;73:34-48. Epub 2018 Nov 1.

Institute of Informatics, Department of Theoretical Informatics, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address:

Homeobox genes are widely considered the major protagonists of embryonic development and tissue formation. For the past decades, it was established that the deregulation of these genes is intimately related to developmental abnormalities and a broad range of diseases in adults. Since the proper regulation and expression of homeobox genes are necessary for a successful developmental program and tissue function, their relation to DNA repair mechanisms become a necessary discussion. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183027
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http://dx.doi.org/10.1016/j.dnarep.2018.10.007DOI Listing
January 2019
8 Reads

Processing of N-substituted formamidopyrimidine DNA adducts by DNA glycosylases NEIL1 and NEIL3.

DNA Repair (Amst) 2019 Jan 5;73:49-54. Epub 2018 Nov 5.

Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239, United States; Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, United States; Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR 97239, United States. Electronic address:

A variety of agents cause DNA base alkylation damage, including the known hepatocarcinogen aflatoxin B (AFB) and chemotherapeutic drugs derived from nitrogen mustard (NM). The N7 site of guanine is the primary site of alkylation, with some N7-deoxyguanosine adducts undergoing imidazole ring-opening to stable mutagenic N-alkyl formamidopyrimidine (Fapy-dG) adducts. These adducts exist as a mixture of canonical β- and unnatural α-anomeric forms. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183023
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http://dx.doi.org/10.1016/j.dnarep.2018.11.001DOI Listing
January 2019
12 Reads

Werner syndrome (WRN) DNA helicase and base excision repair (BER) factors maintain endothelial homeostasis.

DNA Repair (Amst) 2019 Jan 28;73:17-27. Epub 2018 Oct 28.

Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstrasse 5, D-40225, Düsseldorf, Germany. Electronic address:

The accelerated ageing disease Werner Syndrome (WRN) is characterized by pronounced atherosclerosis. Here, we investigated the influence of WRN downregulation on the functionality of non-replicating human endothelial cells. RNAi-mediated downregulation of WRN reduces cell motility and enhances the expression of factors regulating adhesion, inflammation, hemostasis and vasomotor tone. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.10.005DOI Listing
January 2019
1 Read

Deciphering phenotypic variance in different models of DNA-PKcs deficiency.

DNA Repair (Amst) 2019 Jan 30;73:7-16. Epub 2018 Oct 30.

College of Veterinary Medicine, Department of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA. Electronic address:

DNA-PKcs deficiency has been studied in numerous animal models and cell culture systems. In previous studies of kinase inactivating mutations in cell culture systems, ablation of DNA-PK's catalytic activity results in a cell phenotype that is virtually indistinguishable from that ascribed to complete loss of the enzyme. However, a recent compelling study demonstrates a remarkably more severe phenotype in mice harboring a targeted disruption of DNA-PK's ATP binding site as compared to DNA-PKcs deficient mice. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312468PMC
January 2019
9 Reads

The endonuclease domain of Bacillus subtilis MutL is functionally asymmetric.

DNA Repair (Amst) 2019 Jan 24;73:1-6. Epub 2018 Oct 24.

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada; Department of Biochemistry, McGill University, Montreal, QC, Canada. Electronic address:

DNA mismatch repair is an evolutionarily conserved repair pathway that corrects replication errors. In most prokaryotes and all eukaryotes, the mismatch repair protein MutL is a sequence-unspecific endonuclease that nicks the newly synthesized strand and marks it for repair. Although the sequence of the endonuclease domain of MutL is not conserved, eukaryotic MutLα and prokaryotic MutL share four conserved motifs that define the endonuclease site of the protein. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.10.003DOI Listing
January 2019
15 Reads

An RNAi screen in human cell lines reveals conserved DNA damage repair pathways that mitigate formaldehyde sensitivity.

DNA Repair (Amst) 2018 Dec 9;72:1-9. Epub 2018 Oct 9.

Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, 97239, United States; Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, 97239, United States. Electronic address:

Formaldehyde is a ubiquitous DNA damaging agent, with human exposures occurring from both exogenous and endogenous sources. Formaldehyde exposure can result in multiple types of DNA damage, including DNA-protein crosslinks and thus, is representative of other exposures that induce DNA-protein crosslinks such as cigarette smoke, automobile exhaust, wood smoke, metals, ionizing radiation, and certain chemotherapeutics. Our objective in this study was to identify the genes necessary to mitigate formaldehyde toxicity following chronic exposure in human cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.10.002DOI Listing
December 2018
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Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype.

DNA Repair (Amst) 2018 Dec 11;72:10-17. Epub 2018 Oct 11.

The David and Inez Myers Laboratory for Cancer Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, New York, United States. Electronic address:

The genome instability syndrome, ataxia-telangiectasia (A-T) is caused by null mutations in the ATM gene, that lead to complete loss or inactivation of the gene's product, the ATM protein kinase. ATM is the primary mobilizer of the cellular response to DNA double-strand breaks (DSBs) - a broad signaling network in which many components are ATM targets. The major clinical feature of A-T is cerebellar atrophy, characterized by relentless loss of Purkinje and granule cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.10.001DOI Listing
December 2018
9 Reads

Base excision repair capacity as a determinant of prognosis and therapy response in colon cancer patients.

DNA Repair (Amst) 2018 Dec 1;72:77-85. Epub 2018 Oct 1.

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 323 00, Pilsen, Czech Republic. Electronic address:

The DNA-damaging agent 5-fluorouracil represents the most commonly used chemotherapeutic drug for colorectal cancer patients. DNA lesions associated with 5-fluorouracil therapy are primarily repaired by base excision repair (BER) and mismatch repair (MMR) pathways. Published evidence suggests that the individual DNA repair capacity (DRC) may affect a patient's prognosis and response to chemotherapy. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.006DOI Listing
December 2018
2 Reads

Cutting-edge perspectives in genomic maintenance V.

DNA Repair (Amst) 2018 11 25;71:1-2. Epub 2018 Sep 25.

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http://dx.doi.org/10.1016/j.dnarep.2018.09.012DOI Listing
November 2018
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Impact of DNA lesion repair, replication and formation on the mutational spectra of environmental carcinogens: Aflatoxin B as a case study.

DNA Repair (Amst) 2018 11 25;71:12-22. Epub 2018 Aug 25.

Departments of Biological Engineering, Chemistry and The Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:

In a multicellular organism, somatic mutations represent a permanent record of the past chemical and biochemical perturbations experienced by a cell in its local microenvironment. Akin to a perpetual recording device, with every replication, genomic DNA accumulates mutations in patterns that reflect: i) the sequence context-dependent formation of DNA damage, due to environmental or endogenous reactive species, including spontaneous processes; ii) the activity of DNA repair pathways, which, depending on the type of lesion, can erase, ignore or exacerbate the mutagenic consequences of that DNA damage; and iii) the choice of replication machinery that synthesizes the nascent genomic copy. These three factors result in a richly contoured sequence context-dependent mutational spectrum that, from appearances, is distinct for most individual forms of DNA damage. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340726PMC
November 2018
2 Reads

Involvement of transcription-coupled repair factor Mfd and DNA helicase UvrD in mutational processes in Pseudomonas putida.

DNA Repair (Amst) 2018 Dec 26;72:18-27. Epub 2018 Sep 26.

Department of Genetics, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia Street, 51010 Tartu, Estonia. Electronic address:

Stalled RNA polymerases (RNAPs) pose an obstacle for the replicating complexes, which could lead to transcription-replication conflicts and result in genetic instability. Stalled RNAPs and DNA lesions blocking RNAP elongation are removed by transcription-coupled repair (TCR), the process which in bacteria is mediated by TCR factor Mfd and helicase UvrD. Although the mechanism of TCR has been extensively studied, its role in mutagenesis is still obscure. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.011DOI Listing
December 2018
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Replication protein A as a modulator of the poly(ADP-ribose)polymerase 1 activity.

DNA Repair (Amst) 2018 Dec 24;72:28-38. Epub 2018 Sep 24.

Institute of Chemical Biology and Fundamental Medicine, Lavrentiev av. 8, Novosibirsk, 630090, Russia; Department of Natural Sciences, Novosibirsk State University, 1 Pirogov Street, Novosibirsk, 630090, Russia. Electronic address:

Replication protein A contributes to all major pathways of DNA metabolism and is a target for post-translation modifications, including poly(ADP-ribosyl)ation catalyzed by PARP1. Here we demonstrate that the efficiency of RPA poly(ADP-ribosyl)ation strongly depends on the structure of DNA used for PARP1 activation and on the polarity of RPA binding. Moreover, RPA influences PARP1 activity, and this effect also depends on DNA structure: RPA inhibits PAR synthesis catalyzed by PARP1 in the presence of ssDNA and stimulates it in the presence of a DNA duplex, in particular that containing a nick or a gap. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.010DOI Listing
December 2018
22 Reads

Regulated acetylation and deacetylation of H4 K16 is essential for efficient NER in Saccharomyces cerevisiae.

DNA Repair (Amst) 2018 Dec 22;72:39-55. Epub 2018 Sep 22.

Department of Biotechnology, St. Xavier's College, 30, Mother Teresa Sarani, Kolkata, 700016, India. Electronic address:

Acetylation status of H4 K16, a residue in the histone H4 N-terminal tail plays a unique role in regulating chromatin structure and function. Here we show that, during UV-induced nucleotide excision repair H4 K16 gets hyperacetylated following an initial phase of hypoacetylation. Disrupting H4 K16 acetylation-deacetylation by mutating H4 K16 to R (deacetylated state) or Q (acetylated state) leads to compromised chromatin functions. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.009DOI Listing
December 2018
2 Reads

Nucleosomes and the three glycosylases: High, medium, and low levels of excision by the uracil DNA glycosylase superfamily.

DNA Repair (Amst) 2018 Dec 20;72:56-63. Epub 2018 Sep 20.

Department of Chemistry, Brown University, Providence, RI, 02912, United States. Electronic address:

Human cells express the UDG superfamily of glycosylases, which excise uracil (U) from the genome. The three members of this structural superfamily are uracil DNA glycosylase (UNG/UDG), single-strand selective monofunctional uracil DNA glycosylase (SMUG1), and thymine DNA glycosylase (TDG). We previously reported that UDG is efficient at removing U from DNA packaged into nucleosome core particles (NCP) and is minimally affected by the histone proteins when acting on an outward-facing U in the dyad region. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.008DOI Listing
December 2018
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Fluorescent fusions of the N protein of phage Mu label DNA damage in living cells.

DNA Repair (Amst) 2018 Dec 14;72:86-92. Epub 2018 Sep 14.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA; Systems, Synthetic and Physical Biology Program, Rice University, Houston, Texas 77030, USA. Electronic address:

The N protein of phage Mu was indicated from studies in Escherichia coli to hold linear Mu chromosomes in a circular conformation by non-covalent association, and thus suggested potentially to bind DNA double-stranded ends. Because of its role in association with linear Mu DNA, we tested whether fluorescent-protein fusions to N might provide a useful tool for labeling DNA damage including double-strand break (DSB) ends in single cells. We compared N-GFP with a biochemically well documented DSB-end binding protein, the Gam protein of phage Mu, also fused to GFP. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287932PMC
December 2018
12 Reads

Regulation of the initiation of DNA replication in human cells.

DNA Repair (Amst) 2018 Dec 12;72:99-106. Epub 2018 Sep 12.

Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

The origin of species would not have been possible without high fidelity DNA replication and complex genomes evolved with mechanisms that control the initiation of DNA replication at multiple origins on multiple chromosomes such that the genome is duplicated once and only once. The mechanisms that control the assembly and activation of the replicative helicase and the initiation of DNA replication in yeast and Xenopus egg extract systems have been identified and reviewed [1,2]. The goal of this review is to organize currently available data on the mechanisms that control the initiation of DNA replication in human cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261693PMC
December 2018
10 Reads

The hSNM1B/Apollo variant rs11552449 is associated with cellular sensitivity towards mitomycin C and ionizing radiation.

DNA Repair (Amst) 2018 Dec 12;72:93-98. Epub 2018 Sep 12.

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Lipid Clinic at the Interdisciplinary Metabolism Center, Germany; Berlin-Brandenburg Center for Regenerative Medicine (BCRT), Charité University Medicine Berlin, Germany. Electronic address:

The polymorphism rs11552449 (c.181C > T, p.His61Tyr) in the hSNM1B/Apollo gene has been repeatedly shown to be associated with an increased risk for breast cancer. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.004DOI Listing
December 2018
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Rad6-Bre1 mediated histone H2Bub1 protects uncapped telomeres from exonuclease Exo1 in Saccharomyces cerevisiae.

DNA Repair (Amst) 2018 Dec 17;72:64-76. Epub 2018 Sep 17.

The State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China; School of Life Science and Technology, Shanghai Tech University, Shanghai, China. Electronic address:

Histone H2B lysine 123 mono-ubiquitination (H2Bub1), catalyzed by Rad6 and Bre1 in Saccharomyces cerevisiae, modulates chromatin structure and affects diverse cellular functions. H2Bub1 plays roles in telomeric silencing and telomere replication. Here, we have explored a novel role of H2Bub1 in telomere protection at uncapped telomeres in yku70Δ and cdc13-1 cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.007DOI Listing
December 2018
10 Reads

Phosphorylation meets DNA mismatch repair.

DNA Repair (Amst) 2018 Dec 11;72:107-114. Epub 2018 Sep 11.

Medical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany. Electronic address:

DNA mismatch repair (MMR) is a highly conserved process and ensures the removal of mispaired DNA bases and insertion-deletion loops right after replication. For this, a MutSα or MutSβ protein complex recognizes the DNA damage, MutLα nicks the erroneous strand, exonuclease 1 removes the wrong nucleotides, DNA polymerase δ refills the gap and DNA ligase I joins the fragments to seal the nicks and complete the repair process. The failure to accomplish these functions is associated with higher mutation rates and may lead to cancer, which highlights the importance of MMR by the maintenance of genomic stability. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.09.001DOI Listing
December 2018
12 Reads

Mutational spectra and mutational signatures: Insights into cancer aetiology and mechanisms of DNA damage and repair.

Authors:
David H Phillips

DNA Repair (Amst) 2018 11 24;71:6-11. Epub 2018 Aug 24.

MRC-PHE Centre for Environment and Health, King's College London, UK; NIHR Health Protection Research Unit in Health Impact of Environmental Hazards at King's College London in Partnership with Public Health England, Department of Analytical, Environmental and Forensic Sciences, School of Public Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, UK. Electronic address:

Reporter gene assays, in which a single mutation from each experiment can contribute to the assembly of a mutation spectrum for an agent, have provided the basis for understanding the mutational processes induced by mutagenic agents and for providing clues to the origins of mutations in human tumours. More recently exome and whole genome sequencing of human tumours has revealed distinct patterns of mutation that could provide additional clues for the causative origins of cancer. This can be tested by examining the mutational signatures induced in experimental systems by putative cancer-causing agents. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219445PMC
November 2018
6 Reads

Targeting BER enzymes in cancer therapy.

DNA Repair (Amst) 2018 11 25;71:118-126. Epub 2018 Aug 25.

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, S-171 76 Stockholm, Sweden; Sheffield Cancer Centre, Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, UK. Electronic address:

Base excision repair (BER) repairs mutagenic or genotoxic DNA base lesions, thought to be important for both the etiology and treatment of cancer. Cancer phenotypic stress induces oxidative lesions, and deamination products are responsible for one of the most prevalent mutational signatures in cancer. Chemotherapeutic agents induce genotoxic DNA base damage that are substrates for BER, while synthetic lethal approaches targeting BER-related factors are making their way into the clinic. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.08.015DOI Listing
November 2018
15 Reads

Preserving replication fork integrity and competence via the homologous recombination pathway.

DNA Repair (Amst) 2018 11 25;71:135-147. Epub 2018 Aug 25.

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Sussex, BN1 9RQ, UK. Electronic address:

Flaws in the DNA replication process have emerged as a leading driver of genome instability in human diseases. Alteration to replication fork progression is a defining feature of replication stress and the consequent failure to maintain fork integrity and complete genome duplication within a single round of S-phase compromises genetic integrity. This includes increased mutation rates, small and large scale genomic rearrangement and deleterious consequences for the subsequent mitosis that result in the transmission of additional DNA damage to the daughter cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2018.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219450PMC
November 2018
1 Read