2,473 results match your criteria DNA Repair [Journal]


PML nuclear bodies are recruited to persistent DNA damage lesions in an RNF168-53BP1 dependent manner and contribute to DNA repair.

DNA Repair (Amst) 2019 Apr 6;78:114-127. Epub 2019 Apr 6.

Department of Genome Integrity, Institute of Molecular Genetics, v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic; Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czech Republic; Genome Integrity Unit, Danish Cancer Society Research Center, Copenhagen, Denmark; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21, Stockholm, Sweden. Electronic address:

The bulk of DNA damage caused by ionizing radiation (IR) is generally repaired within hours, yet a subset of DNA lesions may persist even for long periods of time. Such persisting IR-induced foci (pIRIF) co-associate with PML nuclear bodies (PML-NBs) and are among the characteristics of cellular senescence. Here we addressed some fundamental questions concerning the nature and determinants of this co-association, the role of PML-NBs at such sites, and the reason for the persistence of DNA damage in human primary cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.04.001DOI Listing

Characterization of a potent dominant negative mutant variant of Rad51 in Ustilago maydis.

DNA Repair (Amst) 2019 Apr 11;78:91-101. Epub 2019 Apr 11.

Department of Microbiology and Immunology, Cornell University, Weill Medical College, New York, NY 10065, USA. Electronic address:

Rad51 serves to maintain and protect integrity of the genome through its actions in DNA repair and replication fork protection. The active form of Rad51 is a nucleoprotein filament consisting of chains of protomer units arranged linearly along single-stranded DNA. In a mutant screen using Ustilago maydis as an experimental system we identified a novel variant of Rad51, in which an amino acid change near the protomer-protomer interaction interface confers a strong trans dominant inhibitory effect on resistance to DNA damaging agents and proficiency in homologous recombination. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.04.003DOI Listing

Deletion of ULS1 confers damage tolerance in sgs1 mutants through a Top3-dependent D-loop mediated fork restart pathway.

DNA Repair (Amst) 2019 Apr 13;78:102-113. Epub 2019 Apr 13.

Department of Pathology and Laboratory Medicine, Philadelphia, Pennsylvania, 19104, United States; Cell and Molecular Biology Group, Biomedical Graduate Studies, Philadelphia, Pennsylvania, 19104, United States; The Institute of Aging, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, United States. Electronic address:

Homologous recombination (HR)-based repair during DNA replication can apparently utilize several partially overlapping repair pathways in response to any given lesion. A key player in HR repair is the Sgs1-Top3-Rmi1 (STR) complex, which is critical for resolving X-shaped recombination intermediates formed following bypass of methyl methanesulfonate (MMS)-induced damage. STR mutants are also sensitive to the ribonucleotide reductase inhibitor, hydroxyurea (HU), but unlike MMS treatment, HU treatment is not accompanied by X-structure accumulation, and it is thus unclear how STR functions in this context. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.04.005DOI Listing

Epigenetically modified N-methyladenine inhibits DNA replication by human DNA polymerase η.

DNA Repair (Amst) 2019 Mar 28;78:81-90. Epub 2019 Mar 28.

Key Laboratory of Environment and Female Reproductive Health, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

N-methyladenine (6mA), as a newly reported epigenetic marker, plays significant roles in regulation of various biological processes in eukaryotes. However, the effect of 6mA on human DNA replication remain elusive. In this work, we used Y-family human DNA polymerase η as a model to investigate the kinetics of bypass of 6mA by hPol η. 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.2019.03.015DOI Listing
March 2019
3 Reads

Genetic and epigenetic alterations induced by the small-molecule panobinostat: A mechanistic study at the chromosome and gene levels.

DNA Repair (Amst) 2019 Mar 23;78:70-80. Epub 2019 Mar 23.

College of Pharmacy, Pharmacology and Toxicology Department, King Saud University, Riyadh, Saudi Arabia; College of Pharmacy, Pharmacology and Toxicology Department, Al-Azhar University, Cairo, Egypt. Electronic address:

Increasing evidence supports the role of genetic and epigenetic alterations in a wide variety of human diseases, including cancer. Assessment of these alterations is hence essential for estimating the hazardous effects of human exposure to medications. Panobinostat received US Food and Drug Administration's approval in 2015 for treatment of certain tumors and its usefulness as part of a strategy to treat other diseases, such as human immunodeficiency virus infection, is currently investigated. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.008DOI Listing

Genome instability consequences of RNase H2 Aicardi-Goutières syndrome alleles.

DNA Repair (Amst) 2019 Apr 4. Epub 2019 Apr 4.

Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. Electronic address:

The RNase H2 complex is a conserved heterotrimeric enzyme that degrades RNA:DNA hybrids and promotes excision of rNMPs misincorporated during DNA replication. Failure to remove ribonucleotides from DNA leads to genomic instability in yeast and humans. The monogenic Aicardi-Goutières syndrome (AGS) results from mutation in one of several genes, among which are those encoding the RNase H2 subunits. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864193000
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http://dx.doi.org/10.1016/j.dnarep.2019.04.002DOI Listing
April 2019
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The mismatch repair-dependent DNA damage response: Mechanisms and implications.

DNA Repair (Amst) 2019 Apr 1;78:60-69. Epub 2019 Apr 1.

Center for Molecular Oncology, UConn Health, Farmington, CT 06030, USA. Electronic address:

An important role for the DNA mismatch repair (MMR) pathway in maintaining genomic stability is embodied in its conservation through evolution and the link between loss of MMR function and tumorigenesis. The latter is evident as inheritance of mutations within the major MMR genes give rise to the cancer predisposition condition, Lynch syndrome. Nonetheless, how MMR loss contributes to tumorigenesis is not completely understood. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.009DOI Listing
April 2019
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The three Endonuclease III variants of Deinococcus radiodurans possess distinct and complementary DNA repair activities.

DNA Repair (Amst) 2019 Mar 28;78:45-59. Epub 2019 Mar 28.

Univ. Grenoble Alpes, CNRS, CEA, IBS, F-38000 Grenoble, France. Electronic address:

Endonuclease III (EndoIII) is a bifunctional DNA glycosylase that removes oxidized pyrimidines from DNA. The genome of Deinococcus radiodurans encodes for an unusually high number of DNA glycosylases, including three EndoIII enzymes (drEndoIII1-3). Here, we compare the properties of these enzymes to those of their well-studied homologues from E. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.014DOI Listing
March 2019
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Ionizing radiation-induced growth in soft agar is associated with miR-21 upregulation in wild-type and DNA double strand break repair deficient cells.

DNA Repair (Amst) 2019 Mar 23;78:37-44. Epub 2019 Mar 23.

Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, GA, United States. Electronic address:

DNA double strand breaks (DSBs) are a severe threat to genome integrity and a potential cause of tumorigenesis, which is a multi-stage process and involves many factors including the mutation of oncogenes and tumor suppressors, some of which are transcribed microRNAs (miRNAs). Among more than 2000 known miRNAs, miR-21 is a unique onco-miRNA that is highly expressed in almost all types of human tumors and is associated with tumorigenesis through its multiple targets. However, it remains unclear whether there is any functional link between DSBs and miR-21 expression and, if so, does the link contribute to DSB-induced genomic instability/tumorigenesis. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.012DOI Listing
March 2019
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Bacillus subtilis RarA acts at the interplay between replication and repair-by-recombination.

DNA Repair (Amst) 2019 Mar 21;78:27-36. Epub 2019 Mar 21.

Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CNB-CSIC, 3 Darwin St., 28049, Madrid, Spain. Electronic address:

Bacterial RarA is thought to play crucial roles in the cellular response to blocked replication forks. We show that lack of Bacillus subtilis RarA renders cells very sensitive to HO, but not to methyl methane sulfonate or 4-nitroquinoline-1-oxide. RarA is epistatic to RecA in response to DNA damage. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.010DOI Listing
March 2019
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Role of Y-family translesion DNA polymerases in replication stress: Implications for new cancer therapeutic targets.

DNA Repair (Amst) 2019 Mar 29;78:20-26. Epub 2019 Mar 29.

Department of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA. Electronic address:

DNA replication stress, defined as the slowing or stalling of replication forks, is considered an emerging hallmark of cancer and a major contributor to genomic instability associated with tumorigenesis (Macheret and Halazonetis, 2015). Recent advances have been made in attempting to target DNA repair factors involved in alleviating replication stress to potentiate genotoxic treatments. Various inhibitors of ATR and Chk1, the two major kinases involved in the intra-S-phase checkpoint, are currently in Phase I and II clinical trials [2]. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.016DOI Listing
March 2019
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Genetic identification and characterization of three genes that prevent accumulation of oxidative DNA damage in Drosophila adult tissues.

DNA Repair (Amst) 2019 Mar 3;78:7-19. Epub 2019 Mar 3.

Department of Insect Biomedical Research, Center for Advanced Insect Research Promotion, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-0962, Japan. Electronic address:

Reactive oxygen species generated in the process of energy production represent a major cause of oxidative DNA damage. Production of the oxidized guanine base, 8-oxo-guanine (8-oxoG), results in mismatched pairing with adenine and subsequently leads to G:C to T:A transversions after DNA replication. Our previous study demonstrated that Drosophila CG1795 encodes an ortholog of Ogg1, which is essential for the elimination of 8-oxoG. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.013DOI Listing
March 2019
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Identification of a miniature Sae2/Ctp1/CtIP ortholog from Paramecium tetraurelia required for sexual reproduction and DNA double-strand break repair.

DNA Repair (Amst) 2019 May 22;77:96-108. Epub 2019 Mar 22.

Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland. Electronic address:

DNA double-strand breaks (DSBs) induced by genotoxic agents can cause cell death or contribute to chromosomal instability, a major driving force of cancer. By contrast, Spo11-dependent DSBs formed during meiosis are aimed at generating genetic diversity. In eukaryotes, CtIP and the Mre11 nuclease complex are essential for accurate processing and repair of both unscheduled and programmed DSBs by homologous recombination (HR). Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.011DOI Listing
May 2019
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Polymorphisms of the DNA repair gene EXO1 modulate cognitive aging in old adults in a Taiwanese population.

DNA Repair (Amst) 2019 Mar 25;78:1-6. Epub 2019 Mar 25.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Evidence indicates that the age-related neuropathological mechanisms associated with DNA repair genes may contribute to cognitive aging and Alzheimer's disease. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within 155 DNA repair genes may be linked to cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 3,730 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.013DOI Listing
March 2019
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SWI/SNF: Complex complexes in genome stability and cancer.

DNA Repair (Amst) 2019 May 15;77:87-95. Epub 2019 Mar 15.

Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands. Electronic address:

SWI/SNF complexes are among the most studied ATP-dependent chromatin remodeling complexes, mostly due to their critical role in coordinating chromatin architecture and gene expression. Mutations in genes encoding SWI/SNF subunits are frequently observed in a large variety of human cancers, suggesting that one or more of the multiple SWI/SNF functions protect against tumorigenesis. Chromatin remodeling is an integral component of the DNA damage response (DDR), which safeguards against DNA damage-induced genome instability and tumorigenesis by removing DNA damage through interconnected DNA repair and signaling pathways. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.007DOI Listing

Mechanisms underlying aflatoxin-associated mutagenesis - Implications in carcinogenesis.

DNA Repair (Amst) 2019 May 7;77:76-86. Epub 2019 Mar 7.

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:

Chronic dietary exposure to aflatoxin B (AFB), concomitant with hepatitis B infection is associated with a significant increased risk for hepatocellular carcinomas (HCCs) in people living in Southeast Asia and sub-Saharan Africa. Human exposures to AFB occur through the consumption of foods that are contaminated with pervasive molds, including Aspergillus flavus. Even though dietary exposures to aflatoxins constitute the second largest global environmental risk factor for cancer development, there are still significant questions concerning the molecular mechanisms driving carcinogenesis and what factors may modulate an individual's risk for HCC. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.004DOI Listing
May 2019
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The invariant glutamate of human PrimPol DxE motif is critical for its Mn-dependent distinctive activities.

DNA Repair (Amst) 2019 May 14;77:65-75. Epub 2019 Mar 14.

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM) c/Nicolás Cabrera 1, Cantoblanco, 28049, Madrid, Spain. Electronic address:

PrimPol is a human primase/polymerase specialized in downstream repriming of stalled forks during both nuclear and mitochondrial DNA replication. Like most primases and polymerases, PrimPol requires divalent metal cations, as Mg or Mn, used as cofactors for catalysis. However, little is known about the consequences of using these two metal cofactors in combination, which would be the most physiological scenario during PrimPol-mediated reactions, and the individual contribution of the putative carboxylate residues (Asp, Glu and Asp) acting as metal ligands. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.006DOI Listing

Optimization of the alkaline comet assay for easy repair capacity quantification of oxidative DNA damage in PBMC from human volunteers using aphidicolin block.

DNA Repair (Amst) 2019 May 14;77:58-64. Epub 2019 Mar 14.

Molecular Preventive Medicine, University Medical Center and Faculty of Medicine, University of Freiburg, Breisacher Straße 115b, 79106 Freiburg im Breisgau, Germany. Electronic address:

Assessment of DNA repair capacity (DRC) upon ex vivo challenge of peripheral blood mononuclear cells (PBMC) with oxidative damage inducing agents, as evaluated by the comet assay, is widely used as biomarker to assess the antioxidant status in human studies. Here, the alkaline comet assay was now optimized for easy and time saving detection of repair capacity upon oxidative stress-induced DNA damage using the DNA polymerase inhibitor aphidicolin (APC) to block repair of hydrogen peroxide (HO) induced DNA damage. Addition of a DMSO-containing DNA damage stop solution was found suitable to replace washing steps for HO removal before APC block. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.005DOI Listing

Bacillus subtilis RadA/Sms contributes to chromosomal transformation and DNA repair in concert with RecA and circumvents replicative stress in concert with DisA.

DNA Repair (Amst) 2019 May 4;77:45-57. Epub 2019 Mar 4.

Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CNB-CSIC, Darwin Str. 3, 28049 Madrid, Spain. Electronic address:

Bacillus subtilis radA is epistatic to disA and recA genes in response to methyl methane sulfonate- and 4-nitroquinoline-1-oxide-induced DNA damage. We show that ΔradA cells were sensitive to mitomycin C- and HO-induced damage and impaired in natural chromosomal transformation, whereas cells lacking DisA were not. RadA/Sms mutants in the conserved H1 (K104A and K104R) or KNRFG (K255A and K255R) motifs fail to rescue the sensitivity of ΔradA in response to the four different DNA damaging agents. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.002DOI Listing

Deoxyuracil in DNA and disease: Genomic signal or managed situation?

DNA Repair (Amst) 2019 May 27;77:36-44. Epub 2019 Feb 27.

Graduate Field of Biochemistry, Molecular and Cellular Biology, Cornell University, Ithaca, NY, 14853, USA; Division of Nutritional Sciences, Cornell University, 127 Savage Hall, Ithaca, NY, 14853, USA. Electronic address:

Genomic instability is implicated in the etiology of several deleterious health outcomes including megaloblastic anemia, neural tube defects, and neurodegeneration. Uracil misincorporation and its repair are known to cause genomic instability by inducing DNA strand breaks leading to apoptosis, but there is emerging evidence that uracil incorporation may also result in broader modifications of gene expression, including: changes in transcriptional stalling, strand break-mediated transcriptional upregulation, and direct promoter inhibition. The factors that influence uracil levels in DNA are cytosine deamination, de novo thymidylate (dTMP) biosynthesis, salvage dTMP biosynthesis, dUTPase, and DNA repair. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.014DOI Listing

Metastasis suppressor NME1 promotes non-homologous end joining of DNA double-strand breaks.

DNA Repair (Amst) 2019 May 4;77:27-35. Epub 2019 Mar 4.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing 102206, China; Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC, 20037, USA; George Washington University Cancer Center, Washington, DC, 20052, USA; Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430062, China. Electronic address:

NME1 (also known as NM23-H1) was the first identified tumor metastasis suppressor, which has been reported to link with genomic stability maintenance and cancer. However its underlying mechanisms are still not fully understood. Here we find that NME1 is required for non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). 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.2019.03.003DOI Listing
May 2019
4 Reads

Mechanisms of MTH1 inhibition-induced DNA strand breaks: The slippery slope from the oxidized nucleotide pool to genotoxic damage.

DNA Repair (Amst) 2019 May 2;77:18-26. Epub 2019 Mar 2.

Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604, United States. Electronic address:

Unlike normal tissues, tumor cells possess a propensity for genomic instability, resulting from elevated oxidant levels produced by oncogenic signaling and aberrant cellular metabolism. Thus, targeting mechanisms that protect cancer cells from the tumor-inhibitory consequences of their redox imbalance and spontaneous DNA-damaging events is expected to have broad-spectrum efficacy and a high therapeutic index. One critical mechanism for tumor cell protection from oxidant stress is the hydrolysis of oxidized nucleotides. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.03.001DOI Listing

Impeding the single-strand annealing pathway of DNA double-strand break repair by withaferin A-mediated FANCA degradation.

DNA Repair (Amst) 2019 May 27;77:10-17. Epub 2019 Feb 27.

Department of Biochemistry & Molecular Biology, Miami, FL, 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. Electronic address:

FANCA is a key player in the canonical Fanconi anemia (FA) repair pathway. We have recently shown that FANCA also plays an important role in the single-strand annealing sub-pathway (SSA) of DNA double-strand break (DSB) repair by biochemically catalyzing single-strand annealing. Here, we report that a steroidal lactone withaferin A (WA) specifically impedes SSA repair by promoting FANCA downregulation at a sub-micromolar concentration range. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476309PMC
May 2019
1 Read

Crystal structure of the yeast Rad7-Elc1 complex and assembly of the Rad7-Rad16-Elc1-Cul3 complex.

DNA Repair (Amst) 2019 May 22;77:1-9. Epub 2019 Feb 22.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Nucleotide excision repair (NER) is a versatile system that deals with various bulky and helix-distorting DNA lesions caused by UV and environmental mutagens. Based on how lesion recognition occurs, NER has been separated into global genome repair (GGR) and transcription-coupled repair (TCR). The yeast Rad7-Rad16 complex is indispensable for the GGR sub-pathway. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.012DOI Listing

RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination.

DNA Repair (Amst) 2019 04 23;76:99-107. Epub 2019 Feb 23.

University of Pittsburgh School of Medicine, Department of Microbiology and Molecular Genetics, UPMC Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA. Electronic address:

The proficiency of cancer cells to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) is a key determinant in predicting response to targeted therapies such as PARP inhibitors. The RAD51 paralogs work as multimeric complexes and act downstream of BRCA1 to facilitate HR. Numerous epidemiological studies have linked RAD51 paralog mutations with hereditary cancer predisposition. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.008DOI Listing
April 2019
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Role of deubiquitinases in DNA damage response.

DNA Repair (Amst) 2019 04 21;76:89-98. Epub 2019 Feb 21.

Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, United States. Electronic address:

DNA damage response (DDR) serves as an integrated cellular network to detect cellular stress and react by activating pathways responsible for halting cell cycle progression, stimulating DNA damage repair, and initiating apoptosis. Efficient DDR protects cells from genomic instability while defective DDR can allow DNA lesions to go unrepaired, causing permanent mutations that will affect future generations of cells and possibly cause disease conditions such as cancer. Therefore, DDR mechanisms must be tightly regulated in order to ensure organismal health and viability. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183030
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http://dx.doi.org/10.1016/j.dnarep.2019.02.011DOI Listing
April 2019
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Evolution of Base Excision Repair in Entamoeba histolytica is shaped by gene loss, gene duplication, and lateral gene transfer.

DNA Repair (Amst) 2019 04 22;76:76-88. Epub 2019 Feb 22.

Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Km. 9.6 Libramiento Norte Carretera Irapuato-León 36821, Irapuato, Gto, CP 36500, Mexico. Electronic address:

During its life cycle, the protist parasite Entamoeba histolytica encounters reactive oxygen and nitrogen species that alter its genome. Base excision repair (BER) is one of the most important pathways for the repair of DNA base lesions. Analysis of the E. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.009DOI Listing
April 2019
2 Reads

Distinct response of adult neural stem cells to low versus high dose ionising radiation.

DNA Repair (Amst) 2019 04 18;76:70-75. Epub 2019 Jan 18.

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.

Radiosusceptibility is the sensitivity of a biological organism to ionising radiation (IR)-induced carcinogenesis, an outcome of IR exposure relevant following low doses. The tissue response is strongly influenced by the DNA damage response (DDR) activated in stem and progenitor cells. We previously reported that in vivo exposure to 2 Gy X-rays activates apoptosis, proliferation arrest and premature differentiation in neural progenitor cells (transit amplifying cells and neuroblasts) but not in neural stem cells (NSCs) of the largest neurogenic region of the adult brain, the subventricular zone (SVZ). Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.01.004DOI Listing
April 2019
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A new perspective on oxidation of DNA repair proteins and cancer.

DNA Repair (Amst) 2019 04 18;76:60-69. Epub 2019 Feb 18.

Department of Therapeutic Radiology and Department of Genetics, Yale University School of Medicine, New Haven, CT, 06520, United States.

Reactive oxygen and nitrogen species (RONS) are formed as byproducts of many endogenous cellular processes, in response to infections, and upon exposure to various environmental factors. An increase in RONS can saturate the antioxidation system and leads to oxidative stress. Consequently, macromolecules are targeted for oxidative modifications, including DNA and protein. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419097PMC

POLE proofreading defects: Contributions to mutagenesis and cancer.

DNA Repair (Amst) 2019 04 16;76:50-59. Epub 2019 Feb 16.

Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA; Tulane Cancer Center, Tulane University School of Medicine, 1430 Tulane Ave., New Orleans, LA, USA. Electronic address:

DNA polymerases are uniquely poised to contribute to the elevated mutation burdens seen in many human tumors. These mutations can arise through a number of different polymerase-dependent mechanisms, including intrinsic errors made using template DNA and precursor dNTPs free from chemical modifications, misinsertion events opposite chemically damaged template DNA or insertion events using modified nucleotides. While specific DNA repair polymerases have been known to contribute to tumorigenesis, the role of replication polymerases in mutagenesis in human disease has come into sharp focus over the last decade. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467506PMC
April 2019
1 Read

Cooperation between non-essential DNA polymerases contributes to genome stability in Saccharomyces cerevisiae.

DNA Repair (Amst) 2019 04 6;76:40-49. Epub 2019 Feb 6.

Department of Microbiology and Molecular Genetics, University of California, Davis, One Shields Avenue, Davis, CA 95616-8665, USA; Department of Molecular and Cellular Biology, University of California, Davis, One Shields Avenue, Davis, CA 95616-8665, USA. Electronic address:

DNA polymerases influence genome stability through their involvement in DNA replication, response to DNA damage, and DNA repair processes. Saccharomyces cerevisiae possess four non-essential DNA polymerases, Pol λ, Pol η, Pol ζ, and Rev1, which have varying roles in genome stability. In order to assess the contribution of the non-essential DNA polymerases in genome stability, we analyzed the pol4Δ rev1Δ rev3Δ rad30Δ quadruple mutant in microhomology mediated repair, due to recent studies linking some of these DNA polymerases to this repair pathway. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443415PMC
April 2019
1 Read

USP7: Structure, substrate specificity, and inhibition.

DNA Repair (Amst) 2019 04 16;76:30-39. Epub 2019 Feb 16.

Department of Molecular Biology and Biophysics, UCONN Health, Farmington, CT, USA. Electronic address:

Turnover of cellular proteins is regulated by Ubiquitin Proteasome System (UPS). Components of this pathway, including the proteasome, ubiquitinating enzymes and deubiquitinating enzymes, are highly specialized and tightly regulated. In this mini-review we focus on the de-ubiquitinating enzyme USP7, and summarize latest advances in understanding its structure, substrate specificity and relevance to human cancers. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15687864183030
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http://dx.doi.org/10.1016/j.dnarep.2019.02.005DOI Listing
April 2019
3 Reads

The role of dePARylation in DNA damage repair and cancer suppression.

DNA Repair (Amst) 2019 04 8;76:20-29. Epub 2019 Feb 8.

Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA. Electronic address:

Poly(ADP-ribosyl)ation (PARylation) is a reversible post-translational modification regulating various biological pathways including DNA damage repair (DDR). Rapid turnover of PARylation is critically important for an optimal DNA damage response and maintaining genomic stability. Recent studies show that PARylation is tightly regulated by a group of enzymes that can erase the ADP-ribose (ADPR) groups from target proteins. Read More

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http://dx.doi.org/10.1016/j.dnarep.2019.02.002DOI Listing
April 2019
7 Reads

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

DNA Repair (Amst) 2019 04 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464370PMC

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

DNA Repair (Amst) 2019 04 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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http://dx.doi.org/10.1016/j.dnarep.2019.02.003DOI Listing
April 2019
3 Reads

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 03 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
March 2019
6 Reads

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

DNA Repair (Amst) 2019 03 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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http://dx.doi.org/10.1016/j.dnarep.2019.01.006DOI Listing
March 2019
5 Reads

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

DNA Repair (Amst) 2019 03 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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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 03 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
March 2019
1 Read

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

DNA Repair (Amst) 2019 03 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382538PMC
March 2019
4 Reads

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

DNA Repair (Amst) 2019 02 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 02 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
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Budding yeast Rtt107 prevents checkpoint hyperactivation after replicative stress by limiting DNA damage.

DNA Repair (Amst) 2019 02 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
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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 02 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
17 Reads

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

DNA Repair (Amst) 2019 02 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 02 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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http://dx.doi.org/10.1016/j.dnarep.2018.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366319PMC
February 2019
25 Reads

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

DNA Repair (Amst) 2019 02 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 02 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
14 Reads

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

DNA Repair (Amst) 2019 01 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
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Synthetic lethality between DNA repair factors Xlf and Paxx is rescued by inactivation of Trp53.

DNA Repair (Amst) 2019 01 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