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DNA Repair

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https://www.readbyqxmd.com/read/28437752/dna-repair-and-damage-pathways-in-breast-cancer-development-and-therapy
#1
REVIEW
Maryam Majidinia, Bahman Yousefi
DNA damage/repair constitutes several key pathways working in concert to eliminate DNA lesions and maintain genome stability and integrity. Defective components in DNA damage and repair machinery are an underlying cause for the development and progression of different types of cancers, and breast cancer is no exception. In this paper, we will briefly explain the importance of DNA damage and repair, introduce the current classification schemes for breast cancer, and review the known defects in the repair machinery that have been associated with the risk of breast cancer...
April 21, 2017: DNA Repair
https://www.readbyqxmd.com/read/28448822/hssb1-phosphorylation-is-dynamically-regulated-by-dna-pk-and-ppp-family-protein-phosphatases
#2
Nicholas W Ashton, Nicolas Paquet, Sally L Shirran, Emma Bolderson, Ruvini Kariawasam, Christine Touma, Azadeh Fallahbaghery, Roland Gamsjaeger, Liza Cubeddu, Catherine Botting, Pamela M Pollock, Kenneth J O'Byrne, Derek J Richard
The maintenance of genomic stability is essential for cellular viability and the prevention of diseases such as cancer. Human single-stranded DNA-binding protein 1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA replication forks, as well as in the repair of oxidative DNA lesions and double-strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the ATM kinase is required for hSSB1 stability and efficient DNA repair. The regulation of hSSB1 in other DNA repair pathways has however remained unclear...
April 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28415030/contradictory-roles-of-nrf2-keap1-signaling-pathway-in-cancer-prevention-promotion-and-chemoresistance
#3
REVIEW
Farhad Jeddi, Narges Soozangar, Mohammad Reza Sadeghi, Mohammad Hossein Somi, Nasser Samadi
NF-E2-related factor 2 (Nrf2) protein is a cytosolic transcription factor that regulates antioxidant and stress-related enzymes. Kelch-like ECH-associated protein 1 (Keap1) binds Nrf2 and accelerates ubiquitination and proteasome-dependent degradation of Nrf2. Nrf2 modifies the sensitivity of the cell environment to electrophiles and oxidants by inducing the transcriptional activation of more than 100 detoxification and cytoprotective genes. Prior investigations have found documentary evidence indicating that temporary activation of Nrf2 by pharmaceutical inducers plays a protective role against cancer initiation in normal cells...
April 3, 2017: DNA Repair
https://www.readbyqxmd.com/read/28388461/activation-induced-deoxycytidine-deaminase-structural-basis-for-favoring-wrc-hot-motif-specificities-unique-among-apobec-family-members
#4
LETTER
Phuong Pham, Samir A Afif, Mayuko Shimoda, Kazuhiko Maeda, Nobuo Sakaguchi, Lars C Pedersen, Myron F Goodman
No abstract text is available yet for this article.
March 28, 2017: DNA Repair
https://www.readbyqxmd.com/read/28384494/increased-genome-instability-is-not-accompanied-by-sensitivity-to-dna-damaging-agents-in-aged-yeast-cells
#5
Daniele Novarina, Sara N Mavrova, Georges E Janssens, Irina L Rempel, Liesbeth M Veenhoff, Michael Chang
The budding yeast Saccharomyces cerevisiae divides asymmetrically, producing a new daughter cell from the original mother cell. While daughter cells are born with a full lifespan, a mother cell ages with each cell division and can only generate on average 25 daughter cells before dying. Aged yeast cells exhibit genomic instability, which is also a hallmark of human aging. However, it is unclear how this genomic instability contributes to aging. To shed light on this issue, we investigated endogenous DNA damage in S...
March 23, 2017: DNA Repair
https://www.readbyqxmd.com/read/28351647/apobec3b-cytidine-deaminase-targets-the-non-transcribed-strand-of-trna-genes-in-yeast
#6
Natalie Saini, Steven A Roberts, Joan F Sterling, Ewa P Malc, Piotr A Mieczkowski, Dmitry A Gordenin
Variations in mutation rates across the genome have been demonstrated both in model organisms and in cancers. This phenomenon is largely driven by the damage specificity of diverse mutagens and the differences in DNA repair efficiency in given genomic contexts. Here, we demonstrate that the single-strand DNA-specific cytidine deaminase APOBEC3B (A3B) damages tRNA genes at a 1000-fold higher efficiency than other non-tRNA genomic regions in budding yeast. We found that A3B-induced lesions in tRNA genes were predominantly located on the non-transcribed strand, while no transcriptional strand bias was observed in protein coding genes...
March 21, 2017: DNA Repair
https://www.readbyqxmd.com/read/28385459/wip1-a-candidate-phosphatase-for-cancer-diagnosis-and-treatment
#7
REVIEW
Tayebeh Oghabi Bakhshaiesh, Keivan Majidzadeh-A, Rezvan Esmaeili
The critical regulatory mechanisms in numerous cellular pathways including cell survival and DNA damage response mostly depend on phosphorylation and dephosphorylation of proteins. The serine/threonine phosphatase wild-type p53-induced phosphatase 1 (Wip1) is a growth-promoting phosphatase and its numerous downstream targets are important tumor suppressors. Here, we review the Wip1 activity and its relevance to cancer as an oncoprotein. Consecutive investigations about Wip1 and its relation to cancer is critical, as these studies ultimately contribute to the etiology of cancer...
March 20, 2017: DNA Repair
https://www.readbyqxmd.com/read/28336179/control-of-dna-end-resection-by-yeast-hmo1p-affects-efficiency-of-dna-end-joining
#8
Arvind Panday, LiJuan Xiao, Ashish Gupta, Anne Grove
The primary pathways for DNA double strand break (DSB) repair are homologous recombination (HR) and non-homologous end-joining (NHEJ). The choice between HR and NHEJ is influenced by the extent of DNA end resection, as extensive resection is required for HR but repressive to NHEJ. Conversely, association of the DNA end-binding protein Ku, which is integral to classical NHEJ, inhibits resection. In absence of key NHEJ components, a third repair pathway is exposed; this alternative-end joining (A-EJ) is a highly error-prone process that uses micro-homologies at the breakpoints and is initiated by DNA end resection...
March 9, 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
#9
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
#10
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
#11
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
#12
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
#13
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/28258841/stimulation-of-lactate-receptor-hcar1-affects-cellular-dna-repair-capacity
#14
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/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
#15
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
#16
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/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#17
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
#18
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/28325498/the-role-of-rnase-h2-in-processing-ribonucleotides-incorporated-during-dna-replication
#19
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...
May 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
#20
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...
April 2017: DNA Repair
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