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DNA Repair

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https://www.readbyqxmd.com/read/28325498/the-role-of-rnase-h2-in-processing-ribonucleotides-incorporated-during-dna-replication
#1
Jessica S Williams, Daniel B Gehle, Thomas A Kunkel
Saccharomyces cerevisiae RNase H2 resolves RNA-DNA hybrids formed during transcription and it incises DNA at single ribonucleotides incorporated during nuclear DNA replication. To distinguish between the roles of these two activities in maintenance of genome stability, here we investigate the phenotypes of a mutant of yeast RNase H2 (rnh201-RED; ribonucleotide excision defective) that retains activity on RNA-DNA hybrids but is unable to cleave single ribonucleotides that are stably incorporated into the genome...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28320593/spore-photoproduct-within-dna-is-a-surprisingly-poor-substrate-for-its-designated-repair-enzyme-the-spore-photoproduct-lyase
#2
Linlin Yang, Yajun Jian, Peter Setlow, Lei Li
DNA repair enzymes typically recognize their substrate lesions with high affinity to ensure efficient lesion repair. In UV irradiated endospores, a special thymine dimer, 5-thyminyl-5,6-dihydrothymine, termed the spore photoproduct (SP), is the dominant DNA photolesion, which is rapidly repaired during spore outgrowth mainly by spore photoproduct lyase (SPL) using an unprecedented protein-harbored radical transfer process. Surprisingly, our in vitro studies using SP-containing short oligonucleotides, pUC 18 plasmid DNA, and E...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28292632/the-novel-activation-induced-deoxycytidine-deaminase-aid-mutants-aidv-and-aidv%C3%AE-15-are-defective-in-shm-and-csr
#3
LETTER
Maki Kobayashi, Misao Takemoto, Tasuku Honjo
No abstract text is available yet for this article.
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28292631/probing-the-activity-of-nthl1-orthologs-by-targeting-conserved-amino-acid-residues
#4
Susan M Robey-Bond, Meredith A Benson, Ramiro Barrantes-Reynolds, Jeffrey P Bond, Susan S Wallace
The base excision repair DNA glycosylases, EcoNth and hNTHL1, are homologous, with reported overlapping yet different substrate specificities. The catalytic amino acid residues are known and are identical between the two enzymes although the exact structures of the substrate binding pockets remain to be determined. We sought to explore the sequence basis of substrate differences using a phylogeny-based design of site-directed mutations. Mutations were made for each enzyme in the vicinity of the active site and we examined these variants for glycosylase and lyase activity...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28291710/measurement-of-dna-damage-in-peripheral-blood-by-the-%C3%AE-h2ax-assay-as-predictor-of-colorectal-cancer-risk
#5
Lina Zhao, David W Chang, Yilei Gong, Cathy Eng, Xifeng Wu
The detection of γ-H2AX focus is one of the most sensitive ways to monitor DNA double-strand breaks (DSBs). Although changes in γ-H2AX activity have been studied in tumor cells in colorectal cancer (CRC), changes in peripheral blood lymphocytes (PBLs) have not been examined previously. We hypothesize that higher levels of irradiation-induced γ-H2AX in PBLs may be associated with an elevated risk of colorectal cancer (CRC). In a case-control study, the baseline and ionizing radiation (IR)-induced γ-H2AX levels in PBLs from frequency-matched 320 untreated CRC patients and 320 controls were detected by a laser scanning cytometer-based immunocytochemical method...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28259467/genetic-variants-of-the-dna-repair-genes-from-exome-aggregation-consortium-exac-database-significance-in-cancer
#6
Raima Das, Sankar Kumar Ghosh
DNA repair pathway is a primary defense system that eliminates wide varieties of DNA damage. Any deficiencies in them are likely to cause the chromosomal instability that leads to cell malfunctioning and tumorigenesis. Genetic polymorphisms in DNA repair genes have demonstrated a significant association with cancer risk. Our study attempts to give a glimpse of the overall scenario of the germline polymorphisms in the DNA repair genes by taking into account of the Exome Aggregation Consortium (ExAC) database as well as the Human Gene Mutation Database (HGMD) for evaluating the disease link, particularly in cancer...
February 22, 2017: DNA Repair
https://www.readbyqxmd.com/read/28268090/both-r-loop-removal-and-ribonucleotide-excision-repair-activities-of-rnase-h2-contribute-substantially-to-chromosome-stability
#7
Deborah A Cornelio, Hailey N C Sedam, Jessica A Ferrarezi, Nadia M V Sampaio, Juan Lucas Argueso
Cells carrying deletions of genes encoding H-class ribonucleases display elevated rates of chromosome instability. The role of these enzymes is to remove RNA-DNA associations including persistent mRNA-DNA hybrids (R-loops) formed during transcription, and ribonucleotides incorporated into DNA during replication. RNases H1 and H2 can degrade the RNA component of R-loops, but only RNase H2 can initiate accurate ribonucleotide excision repair (RER). In order to examine the specific contributions of these activities to chromosome stability, we measured rates of loss-of-heterozygosity (LOH) in diploid Saccharomyces cerevisiae yeast strains carrying the rnh201-RED separation-of-function allele, encoding a version of RNase H2 that is RER-defective, but partly retains its other activity...
February 20, 2017: DNA Repair
https://www.readbyqxmd.com/read/28258841/stimulation-of-lactate-receptor-hcar1-affects-cellular-dna-repair-capacity
#8
Waldemar Wagner, Katarzyna D Kania, Wojciech M Ciszewski
Numerous G-protein coupled receptors have been reported to enhance cancer cell survival and resistance to clinically used chemotherapeutics. Recently, hydroxycarboxylic acid receptor 1 (HCAR1) was shown to drive lactate-dependent enhancement of cell survival and metastasis in pancreatic and breast cancers. Furthermore, our previous study confirmed the involvement of HCAR1 in lactate-related enhancement of DNA repair in cervical cancer cells. In the present study, we examined the possible mechanisms of HCAR1-mediated enhancement of DNA repair capacity...
February 20, 2017: DNA Repair
https://www.readbyqxmd.com/read/28254357/rad-adapt-software-for-modelling-clonogenic-assay-data-in-radiation-biology
#9
Yaping Zhang, Kaiqiang Hu, Jan H Beumer, Christopher J Bakkenist, David Z D'Argenio
We present a comprehensive software program, RAD-ADAPT, for the quantitative analysis of clonogenic assays in radiation biology. Two commonly used models for clonogenic assay analysis, the linear-quadratic model and single-hit multi-target model, are included in the software. RAD-ADAPT uses maximum likelihood estimation method to obtain parameter estimates with the assumption that cell colony count data follow a Poisson distribution. The program has an intuitive interface, generates model prediction plots, tabulates model parameter estimates, and allows automatic statistical comparison of parameters between different groups...
February 20, 2017: DNA Repair
https://www.readbyqxmd.com/read/28254358/specific-killing-of-dna-damage-response-deficient-cells-with-inhibitors-of-poly-adp-ribose-glycohydrolase
#10
Polly Gravells, Emma Grant, Kate M Smith, Dominic I James, Helen E Bryant
Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks...
February 17, 2017: DNA Repair
https://www.readbyqxmd.com/read/28254425/the-anti-syn-conformation-of-8-oxo-7-8-dihydro-2-deoxyguanosine-is-modulated-by-bacillus-subtilis-polx-active-site-residues-his255-and-asn263-efficient-processing-of-damaged-3-ends
#11
Olga Zafra, Lucía Pérez de Ayala, Miguel de Vega
8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG) is a major lesion resulting from oxidative stress and found in both DNA and dNTP pools. Such a lesion is usually removed from DNA by the Base Excision Repair (BER), a universally conserved DNA repair pathway. 8oxodG usually adopts the favored and promutagenic syn-conformation at the active site of DNA polymerases, allowing the base to hydrogen bonding with adenine during DNA synthesis. Here, we study the structural determinants that affect the glycosidic torsion-angle of 8oxodGTP at the catalytic active site of the family X DNA polymerase from Bacillus subtilis (PolXBs)...
February 16, 2017: DNA Repair
https://www.readbyqxmd.com/read/28237621/inorganic-arsenic-inhibits-the-nucleotide-excision-repair-pathway-and-reduces-the-expression-of-xpc
#12
Nathaniel Holcomb, Mamta Goswami, Sung Gu Han, Tim Scott, John D'Orazio, David K Orren, C Gary Gairola, Isabel Mellon
Chronic exposure to arsenic, most often through contaminated drinking water, has been linked to several types of cancer in humans, including skin and lung cancer. However, the mechanisms underlying its role in causing cancer are not well understood. There is evidence that exposure to arsenic can enhance the carcinogenicity of UV light in inducing skin cancers and may enhance the carcinogenicity of tobacco smoke in inducing lung cancers. The nucleotide excision repair (NER) pathway removes different types of DNA damage including those produced by UV light and components of tobacco smoke...
February 16, 2017: DNA Repair
https://www.readbyqxmd.com/read/28242054/effects-of-methyl-and-inorganic-mercury-exposure-on-genome-homeostasis-and-mitochondrial-function-in-caenorhabditis-elegans
#13
Lauren H Wyatt, Anthony L Luz, Xiou Cao, Laura L Maurer, Ashley M Blawas, Alejandro Aballay, William K Y Pan, Joel N Meyer
Mercury toxicity mechanisms have the potential to induce DNA damage and disrupt cellular processes, like mitochondrial function. Proper mitochondrial function is important for cellular bioenergetics and immune signaling and function. Reported impacts of mercury on the nuclear genome (nDNA) are conflicting and inconclusive, and mitochondrial DNA (mtDNA) impacts are relatively unknown. In this study, we assessed genotoxic (mtDNA and nDNA), metabolic, and innate immune impacts of inorganic and organic mercury exposure in Caenorhabditis elegans...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#14
Kathrin Weidele, Sascha Beneke, Alexander Bürkle
NAD(+) is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD(+) consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD(+) levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28254426/dna-damage-in-lymphocytes-of-patients-suffering-from-complex-traumatization
#15
Liana M Bergholz, Claudia Subic-Wrana, Daniel Heylmann, Manfred E Beutel, Jörg Wiltink, Bernd Kaina
It has been shown that complex childhood traumatization (CCT) increases the risk for severe somatic and mental disorders. However, the somatic pathways linking maladaptive affect regulation and disease are not understood. Here we tested the hypothesis that traumatic stress is linked to the induction of DNA damage. We isolated peripheral lymphocytes (PBLCs) from blood of healthy donors and patients suffering from CCT. Cells were immobilised on slides and stained with anti-phosphohistone 2AX (γH2AX). The number of γH2AX foci, which are an accepted surrogate marker of DNA double-strand breaks (DSBs), was determined and set in relation to the patient characteristics...
February 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28262582/a-role-for-the-base-excision-repair-enzyme-neil3-in-replication-dependent-repair-of-interstrand-dna-cross-links-derived-from-psoralen-and-abasic-sites
#16
REVIEW
Zhiyu Yang, Maryam Imani Nejad, Jacqueline Gamboa Varela, Nathan E Price, Yinsheng Wang, Kent S Gates
Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are "unhooked" by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link. This process generates a double-strand break, which must be subsequently repaired by homologous recombination. Recent work provided evidence for a new, incision-independent unhooking mechanism involving intrusion of a base excision repair (BER) enzyme, NEIL3, into the world of cross-link repair...
April 2017: DNA Repair
https://www.readbyqxmd.com/read/28209516/movement-of-the-%C3%AE-hairpin-in-the-third-zinc-binding-module-of-uvra-is-required-for-dna-damage-recognition
#17
Thanyalak Kraithong, Ketsaraphorn Channgam, Ornchuma Itsathitphaisarn, Montip Tiensuwan, David Jeruzalmi, Danaya Pakotiprapha
Nucleotide excision repair (NER) is distinguished from other DNA repair pathways by its ability to process various DNA lesions. In bacterial NER, UvrA is the key protein that detects damage and initiates the downstream NER cascade. Although it is known that UvrA preferentially binds to damaged DNA, the mechanism for damage recognition is unclear. A β-hairpin in the third Zn-binding module (Zn3hp) of UvrA has been suggested to undergo a conformational change upon DNA binding, and proposed to be important for damage sensing...
March 2017: DNA Repair
https://www.readbyqxmd.com/read/28209515/cell-type-specific-role-of-the-rna-binding-protein-nono-in-the-dna-double-strand-break-response-in-the-mouse-testes
#18
Shuyi Li, Feng-Jue Shu, Zhentian Li, Lahcen Jaafar, Shourong Zhao, William S Dynan
The tandem RNA recognition motif protein, NONO, was previously identified as a candidate DNA double-strand break (DSB) repair factor in a biochemical screen for proteins with end-joining stimulatory activity. Subsequent work showed that NONO and its binding partner, SFPQ, have many of the properties expected for bona fide repair factors in cell-based assays. Their contribution to the DNA damage response in intact tissue in vivo has not, however, been demonstrated. Here we compare DNA damage sensitivity in the testes of wild-type mice versus mice bearing a null allele of the NONO homologue (Nono (gt))...
March 2017: DNA Repair
https://www.readbyqxmd.com/read/28189416/repair-of-oxidative-dna-damage-in-saccharomyces-cerevisiae
#19
REVIEW
Jisha Chalissery, Deena Jalal, Zeina Al-Natour, Ahmed H Hassan
Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomolecules including DNA and consequently activates various DNA repair pathways. The nature of DNA damage and the cell cycle stage at which DNA damage occurs determine the appropriate repair pathway to rectify the damage. Oxidized DNA bases are primarily repaired by base excision repair and nucleotide incision repair. Nucleotide excision repair acts on lesions that distort DNA helix, mismatch repair on mispaired bases, and homologous recombination and non-homologous end joining on double stranded breaks...
March 2017: DNA Repair
https://www.readbyqxmd.com/read/28185850/an-improved-method-for-the-detection-of-nucleotide-excision-repair-factors-at-local-uv-dna-damage-sites
#20
Ilaria Dutto, Ornella Cazzalini, Lucia Anna Stivala, Ennio Prosperi
Among different DNA repair processes that cells use to face with DNA damage, nucleotide excision repair (NER) is particularly important for the removal of a high variety of lesions, including those generated by some antitumor drugs. A number of factors participating in NER, such as the TFIIH complex and the endonuclease XPG are also involved in basal processes, e.g. transcription. For this reason, localization of these factors at DNA damage sites may be difficult. Here we have applied a mild digestion of chromatin with DNase I to improve the in situ extraction necessary to detect chromatin-bound proteins by immunofluorescence...
March 2017: DNA Repair
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