914 results match your criteria uv-induced mutagenesis


DNA polymerase η is a substrate for calpain: A possible mechanism for pol η retention in UV induced replication foci.

J Cell Sci 2021 Jun 3. Epub 2021 Jun 3.

Biotechnologie et Signalisation Cellulaire, Université de Strasbourg, UMR7242, CNRS, Illkirch 67412, France.

DNA polymerase η (pol η) is specifically required for translesion DNA synthesis across ultraviolet radiation-induced DNA lesions. Recruitment of this error-prone DNA polymerase is tightly regulated during replication to avoid mutagenesis and perturbation of fork progression. Here we report that pol η interacts with the calpain small subunit-1 (CAPNS1), in a yeast two-hybrid screening. Read More

View Article and Full-Text PDF

A streamlined solution for processing, elucidating and quality control of cyclobutane pyrimidine dimer sequencing data.

Nat Protoc 2021 04 17;16(4):2190-2212. Epub 2021 Mar 17.

Comprehensive Cancer Center, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.

UV radiation may lead to melanoma and nonmelanoma skin cancers by causing helix-distorting DNA damage such as cyclobutane pyrimidine dimers (CPDs). These DNA lesions, if located in important genes and not repaired promptly, are mutagenic and may eventually result in carcinogenesis. Examining CPD formation and repair processes across the genome can shed light on the mutagenesis mechanisms associated with UV damage in relevant cancers. Read More

View Article and Full-Text PDF

Developmental delay with hypotrophy associated with homozygous functionally relevant REV3L variant.

J Mol Med (Berl) 2021 03 20;99(3):415-423. Epub 2021 Jan 20.

Department of Medical Genetics, Medical University of Warsaw, 02-106, Warsaw, Poland.

REV3L encodes a catalytic subunit of DNA polymerase zeta (Pol zeta) which is essential for the tolerance of DNA damage by inducing translesion synthesis (TLS). So far, the only Mendelian disease associated with REV3L was Moebius syndrome (3 patients with dominant REV3L mutations causing monoallelic loss-of-function were reported). We describe a homozygous ultra-rare REV3L variant (T2753R) identified with whole exome sequencing in a child without Moebius syndrome but with developmental delay, hypotrophy, and dysmorphic features who was born to healthy parents (heterozygous carriers of the variant). Read More

View Article and Full-Text PDF

UV-exposure, endogenous DNA damage, and DNA replication errors shape the spectra of genome changes in human skin.

PLoS Genet 2021 01 14;17(1):e1009302. Epub 2021 Jan 14.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle Park, North Carolina, United States of America.

Human skin is continuously exposed to environmental DNA damage leading to the accumulation of somatic mutations over the lifetime of an individual. Mutagenesis in human skin cells can be also caused by endogenous DNA damage and by DNA replication errors. The contributions of these processes to the somatic mutation load in the skin of healthy humans has so far not been accurately assessed because the low numbers of mutations from current sequencing methodologies preclude the distinction between sequencing errors and true somatic genome changes. Read More

View Article and Full-Text PDF
January 2021

Variable interplay of UV-induced DNA damage and repair at transcription factor binding sites.

Nucleic Acids Res 2021 01;49(2):891-901

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.

An abnormally high rate of UV-light related mutations appears at transcription factor binding sites (TFBS) across melanomas. The binding of transcription factors (TFs) to the DNA impairs the repair of UV-induced lesions and certain TFs have been shown to increase the rate of generation of these lesions at their binding sites. However, the precise contribution of these two elements to the increase in mutation rate at TFBS in these malignant cells is not understood. Read More

View Article and Full-Text PDF
January 2021

Non-recombinogenic roles for Rad52 in translesion synthesis during DNA damage tolerance.

EMBO Rep 2021 01 2;22(1):e50410. Epub 2020 Dec 2.

Department of Genome Biology, Andalusian Molecular Biology and Regenerative Medicine Center (CABIMER), CSIC-University of Seville-University Pablo de Olavide, Seville, Spain.

DNA damage tolerance relies on homologous recombination (HR) and translesion synthesis (TLS) mechanisms to fill in the ssDNA gaps generated during passing of the replication fork over DNA lesions in the template. Whereas TLS requires specialized polymerases able to incorporate a dNTP opposite the lesion and is error-prone, HR uses the sister chromatid and is mostly error-free. We report that the HR protein Rad52-but not Rad51 and Rad57-acts in concert with the TLS machinery (Rad6/Rad18-mediated PCNA ubiquitylation and polymerases Rev1/Pol ζ) to repair MMS and UV light-induced ssDNA gaps through a non-recombinogenic mechanism, as inferred from the different phenotypes displayed in the absence of Rad52 and Rad54 (essential for MMS- and UV-induced HR); accordingly, Rad52 is required for efficient DNA damage-induced mutagenesis. Read More

View Article and Full-Text PDF
January 2021

Atypical UV Photoproducts Induce Non-canonical Mutation Classes Associated with Driver Mutations in Melanoma.

Cell Rep 2020 11;33(7):108401

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

Somatic mutations in skin cancers and other ultraviolet (UV)-exposed cells are typified by C>T and CC>TT substitutions at dipyrimidine sequences; however, many oncogenic "driver" mutations in melanoma do not fit this UV signature. Here, we use genome sequencing to characterize mutations in yeast repeatedly irradiated with UV light. Analysis of ~50,000 UV-induced mutations reveals abundant non-canonical mutations, including T>C, T>A, and AC>TT substitutions. Read More

View Article and Full-Text PDF
November 2020

DNA polymerase eta: A potential pharmacological target for cancer therapy.

J Cell Physiol 2021 Jun 13;236(6):4106-4120. Epub 2020 Nov 13.

Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.

In the last two decades, intensive research has been carried out to improve the survival rates of cancer patients. However, the development of chemoresistance that ultimately leads to tumor relapse poses a critical challenge for the successful treatment of cancer patients. Many cancer patients experience tumor relapse and ultimately die because of treatment failure associated with acquired drug resistance. Read More

View Article and Full-Text PDF

Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair.

Nat Commun 2020 09 28;11(1):4868. Epub 2020 Sep 28.

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

DNA damage sensors DDB2 and XPC initiate global genome nucleotide excision repair (NER) to protect DNA from mutagenesis caused by helix-distorting lesions. XPC recognizes helical distortions by binding to unpaired ssDNA opposite DNA lesions. DDB2 binds to UV-induced lesions directly and facilitates efficient recognition by XPC. Read More

View Article and Full-Text PDF
September 2020

Characterization and improvement of curdlan produced by a high-yield mutant of Agrobacterium sp. ATCC 31749 based on whole-genome analysis.

Carbohydr Polym 2020 Oct 30;245:116486. Epub 2020 May 30.

School of Life Sciences, East China Normal University, Shanghai, 200241, PR China. Electronic address:

Curdlan is a bacterial, water-insoluble, linear homopolysaccharide that has been widely used in the food industry. In this study, genome information of strain CGMCC 11546, a UV-induced high-yield mutant of the model curdlan-producing strain Agrobacterium sp. ATCC 31749, was used to investigate the molecular mechanism of curdlan biosynthesis. Read More

View Article and Full-Text PDF
October 2020

Genome-Wide Mapping of UV-Induced DNA Damage with CPD-Seq.

Methods Mol Biol 2020 ;2175:79-94

School of Molecular Biosciences, Washington State University, Pullman, WA, USA.

Exposure to ultraviolet (UV) radiation is the major risk factor for skin cancers. UV induces helix-distorting DNA damage such as cyclobutane pyrimidine dimers (CPDs). If not repaired, CPDs can strongly block DNA and RNA polymerases and cause mutagenesis or cell death. Read More

View Article and Full-Text PDF

Regulation of UV damage repair in quiescent yeast cells.

DNA Repair (Amst) 2020 06 30;90:102861. Epub 2020 Apr 30.

Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA. Electronic address:

Non-growing quiescent cells face special challenges when repairing lesions produced by exogenous DNA damaging agents. These challenges include the global repression of transcription and translation and a compacted chromatin structure. We investigated how quiescent yeast cells regulated the repair of DNA lesions produced by UV irradiation. Read More

View Article and Full-Text PDF

Ultraviolet Mutagenesis Coupled with Next-Generation Sequencing as a Method for Functional Interrogation of Powdery Mildew Genomes.

Mol Plant Microbe Interact 2020 Aug 29;33(8):1008-1021. Epub 2020 Jun 29.

RWTH Aachen University, Institute for Biology I, Unit of Plant Molecular Cell Biology, Worringerweg 1, 52056 Aachen, Germany.

Powdery mildews are obligate biotrophic fungal pathogens causing important diseases of plants worldwide. Very little is known about the requirements for their pathogenicity at the molecular level. This is largely due to the inability to culture these organisms in vitro or to modify them genetically. Read More

View Article and Full-Text PDF

Solar ultraviolet-induced DNA damage response: Melanocytes story in transformation to environmental melanomagenesis.

Environ Mol Mutagen 2020 08 8;61(7):736-751. Epub 2020 May 8.

Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA.

Exposure to sunlight is both beneficial, as it heats the planet to a comfortable temperature, and potentially harmful, since sunlight contains ultraviolet radiation (UVR), which is deemed detrimental for living organisms. Earth's ozone layer plays a vital role in blocking most of the extremely dangerous UVC; however, low frequency/energy UVR (i.e. Read More

View Article and Full-Text PDF

Exome sequencing identifies novel mutation signatures of UV radiation and trichostatin A in primary human keratinocytes.

Sci Rep 2020 03 18;10(1):4943. Epub 2020 Mar 18.

The Hormel Institute, University of Minnesota, Austin, MN, USA.

Canonical ultraviolet (UV) mutation type and spectra are traditionally defined by direct sequencing-based approaches to map mutations in a limited number of representative DNA elements. To obtain an unbiased view of genome wide UV mutation features, we performed whole exome-sequencing (WES) to profile single nucleotide substitutions in UVB-irradiated primary human keratinocytes. Cross comparison of UV mutation profiles under different UVB radiation conditions revealed that T > C transition was highly prevalent in addition to C > T transition. Read More

View Article and Full-Text PDF

Development of an Efficient Transformation System for Halotolerant Yeast CBS767.

Bio Protoc 2019 Sep 5;9(17):e3352. Epub 2019 Sep 5.

Universite Grenoble Alpes, France.

is one of the most osmotolerant and halotolerant yeasts. Further, its association with traditional cheese and meat products imparting special flavors to these products project this yeast with enormous biotechnological potential in the agrofood sector. However, lack of an efficient transformation system in still direct the complementation based assay in mutants for functional analysis of genes. Read More

View Article and Full-Text PDF
September 2019

Vital roles of PCNA K165 modification during C. elegans gametogenesis and embryogenesis.

DNA Repair (Amst) 2019 10 11;82:102688. Epub 2019 Aug 11.

Graduate School of Life Sciences, Tohoku University, Sendai, Japan; Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan. Electronic address:

In eukaryotes, the DNA damage bypass pathway is promoted by ubiquitylation of PCNA at the conserved lysine 164. Using CRISPR-Cas9 system, we introduced amino acid substitution at K165 of C. elegans PCNA that corresponds to K164 in other characterised organisms and examined the contribution of this residue at a variety of stages during development. Read More

View Article and Full-Text PDF
October 2019

Mammalian DNA Polymerase Kappa Activity and Specificity.

Molecules 2019 Aug 1;24(15). Epub 2019 Aug 1.

Department of Chemistry & Chemical Biology, Northeastern University, Boston, MA 02115, USA.

DNA polymerase (pol) kappa is a Y-family translesion DNA polymerase conserved throughout all domains of life. Pol kappa is special6 ized for the ability to copy DNA containing minor groove DNA adducts, especially -dG adducts, as well as to extend primer termini containing DNA damage or mismatched base pairs. Pol kappa generally cannot copy DNA containing major groove modifications or UV-induced photoproducts. Read More

View Article and Full-Text PDF

Transcription-Coupled Repair: From Cells to Single Molecules and Back Again.

J Mol Biol 2019 09 6;431(20):4093-4102. Epub 2019 Jun 6.

Institut Jacques Monod, CNRS and Université Paris 7, Paris Université, Paris, France; Institut de Biologie de l'Ecole normale supérieure, PSL Université, INSERM, CNRS, Paris, France; Horizons 2020 Innovative Training Network, DNAREPAIRMAN, Paris, France.

Transcription-coupled repair is mediated by the Mfd protein. TCR is defined as the preferential repair of DNA lesions in the transcribed strand of actively transcribed genes, and is opposed to the strand-aspecific global genome repair. The Mfd protein mediates TCR by binding to and displacing RNA polymerase, which is stalled at a DNA lesion on the transcribed strand of DNA, then recruiting UvrA and UvrB. Read More

View Article and Full-Text PDF
September 2019

Biochemical reconstitution of UV-induced mutational processes.

Nucleic Acids Res 2019 07;47(13):6769-6782

Department of Biological Sciences, Ohio University, Athens, OH 45701, USA.

We reconstituted two biochemical processes that may contribute to UV-induced mutagenesis in vitro and analysed the mutational profiles in the products. One process is translesion synthesis (TLS) by DNA polymerases (Pol) δ, η and ζ, which creates C>T transitions at pyrimidine dimers by incorporating two dAMPs opposite of the dimers. The other process involves spontaneous deamination of cytosine, producing uracil in pyrimidine dimers, followed by monomerization of the dimers by secondary UV irradiation, and DNA synthesis by Pol δ. Read More

View Article and Full-Text PDF

ImuB and ImuC contribute to UV-induced mutagenesis as part of the SOS regulon in Pseudomonas aeruginosa.

Environ Mol Mutagen 2019 08 30;60(7):594-601. Epub 2019 Apr 30.

Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Química Biológica Ranwel Caputto, Córdoba, Argentina.

DNA damage-induced mutagenesis is a process governed by the SOS system that requires the activity of specialized DNA polymerases. These polymerases, which are devoid of proof-reading activity, serve to increase the probability of survival under stressful conditions in exchange for an error-prone DNA synthesis. As an opportunistic pathogen of humans, Pseudomonas aeruginosa employs adaptive responses that originally evolved for survival in many diverse and often stressful environmental conditions, where the action of error-prone DNA polymerases may be crucial. Read More

View Article and Full-Text PDF

Rad5 Recruits Error-Prone DNA Polymerases for Mutagenic Repair of ssDNA Gaps on Undamaged Templates.

Mol Cell 2019 03 4;73(5):900-914.e9. Epub 2019 Feb 4.

Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON M5S 3E1, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada. Electronic address:

Post-replication repair (PRR) allows tolerance of chemical- and UV-induced DNA base lesions in both an error-free and an error-prone manner. In classical PRR, PCNA monoubiquitination recruits translesion synthesis (TLS) DNA polymerases that can replicate through lesions. We find that PRR responds to DNA replication stress that does not cause base lesions. Read More

View Article and Full-Text PDF

Overproduction of thermoalkalophilic lipase secreted by Bacillus atrophaeus FSHM2 using UV-induced mutagenesis and statistical optimization of medium components.

Prep Biochem Biotechnol 2019 3;49(2):184-191. Epub 2019 Feb 3.

a Pharmaceutics Research Center, Institute of Neuropharmacology , Kerman University of Medical Sciences , Kerman , Iran.

Microbial enzymes of extremophilic origin serve as a vital source of stable industrial enzymes. The present study focused on overproduction of a thermoalkalophilic lipase produced by Bacillus atrophaeus FSHM2 through UV-induced random mutagenesis (5-45 min exposure to UV light) and factorial experimental design augmented to response surface methodology. Firstly, a UV-induced mutant (designated as UV-45) was developed after the exposure of wild strain to UV irradiation for 45 min which was able to secrete 3484. Read More

View Article and Full-Text PDF

Photoprotective and Antigenotoxic Effects of the Flavonoids Apigenin, Naringenin and Pinocembrin.

Photochem Photobiol 2019 07 27;95(4):1010-1018. Epub 2019 Feb 27.

Laboratorio de Microbiología y Mutagénesis Ambiental, Grupo de Investigación en Microbiología y Genética, Escuela de Biología, Universidad Industrial de Santander, Bucaramanga, Colombia.

This work evaluated the photoprotective and antigenotoxic effects against ultraviolet B (UVB) radiation of flavonoid compounds apigenin, naringenin and pinocembrin. The photoprotective efficacy of these compounds was estimated using in vitro photoprotection indices, and the antigenotoxicity against UVB radiation was evaluated using the SOS chromotest and an enzymatic (proteinase K/T4 endonuclease V enzyme) comet assay in UV-treated Escherichia coli and human (HEK-293) cells, respectively. Naringenin and pinocembrin showed maximum UV-absorption peak in UVC and UVB zones, while apigenin showed UV-absorption capability from UVC to UVA range. Read More

View Article and Full-Text PDF

Evaluation of strategies for improving the transgene expression in an oleaginous microalga Scenedesmus acutus.

BMC Biotechnol 2019 01 10;19(1). Epub 2019 Jan 10.

Special Research Unit in Microalgal Molecular Genetics and Functional Genomics (MMGFG), Department of Genetics, Faculty of Science, Kasetsart University, 50 Ngam Wong Wan road, Chatuchak, Bangkok, 10900, Thailand.

Background: Genetic transformation of microalgae has been hampered by inefficient transgene expression, limiting the progress of microalgal biotechnology. Many vector tools and strategies have been developed in recent years to improve transgene expression in the model microalga Chlamydomonas, but these were hardly applied to other microalgae. In this work, naturally-isolated oleaginous microalgae were accessed for genetic transformation, and various expression systems were evaluated in a selected microalga to circumvent inefficient transgene expression. Read More

View Article and Full-Text PDF
January 2019

DNA polymerase η contributes to genome-wide lagging strand synthesis.

Nucleic Acids Res 2019 03;47(5):2425-2435

Department of Medical Biochemistry and Cell Biology, University of Gothenburg, 40530 Gothenburg, Sweden.

DNA polymerase η (pol η) is best known for its ability to bypass UV-induced thymine-thymine (T-T) dimers and other bulky DNA lesions, but pol η also has other cellular roles. Here, we present evidence that pol η competes with DNA polymerases α and δ for the synthesis of the lagging strand genome-wide, where it also shows a preference for T-T in the DNA template. Moreover, we found that the C-terminus of pol η, which contains a PCNA-Interacting Protein motif is required for pol η to function in lagging strand synthesis. Read More

View Article and Full-Text PDF

Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in .

PeerJ 2018 5;6:e6029. Epub 2018 Dec 5.

Groupe «Réparation de l'ADN», Equipe Labellisée par la Ligue Nationale Contre le Cancer, CNRS UMR8200, Université Paris-Sud, Gustave Roussy Cancer Campus, Villejuif, France.

Background: DNA repair is essential to counteract damage to DNA induced by endo- and exogenous factors, to maintain genome stability. However, challenges to the faithful discrimination between damaged and non-damaged DNA strands do exist, such as mismatched pairs between two regular bases resulting from spontaneous deamination of 5-methylcytosine or DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved the mismatch-specific DNA glycosylases that can recognize and remove regular DNA bases in the mismatched DNA duplexes. Read More

View Article and Full-Text PDF
December 2018

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

DNA Repair (Amst) 2019 01 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

View Article and Full-Text PDF
January 2019

A novel role for CRIM1 in the corneal response to UV and pterygium development.

Exp Eye Res 2019 02 24;179:75-92. Epub 2018 Oct 24.

Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, BT52 1SA, UK. Electronic address:

Pterygium is a pathological proliferative condition of the ocular surface, characterised by formation of a highly vascularised, fibrous tissue arising from the limbus that invades the central cornea leading to visual disturbance and, if untreated, blindness. Whilst chronic ultraviolet (UV) light exposure plays a major role in its pathogenesis, higher susceptibility to pterygium is observed in some families, suggesting a genetic component. In this study, a Northern Irish family affected by pterygium but reporting little direct exposure to UV was identified carrying a missense variant in CRIM1 NM_016441. Read More

View Article and Full-Text PDF
February 2019

Sirtuin 1-mediated deacetylation of XPA DNA repair protein enhances its interaction with ATR protein and promotes cAMP-induced DNA repair of UV damage.

J Biol Chem 2018 12 16;293(49):19025-19037. Epub 2018 Oct 16.

From the Markey Cancer Center and

Blunted melanocortin 1 receptor (MC1R) signaling promotes melanocyte genomic instability in part by attenuating cAMP-mediated DNA repair responses, particularly nucleotide excision repair (NER), which recognizes and clears mutagenic photodamage. cAMP-enhanced NER is mediated by interactions between the ataxia telangiectasia-mutated and Rad3-related (ATR) and xeroderma pigmentosum complementation group A (XPA) proteins. We now report a critical role for sirtuin 1 (SIRT1) in regulating ATR-mediated phosphorylation of XPA. Read More

View Article and Full-Text PDF
December 2018