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DNA Repair

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https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#1
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/28209515/cell-type-specific-role-of-the-rna-binding-protein-nono-in-the-dna-double-strand-break-response-in-the-mouse-testes
#2
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))...
February 10, 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
#3
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...
February 7, 2017: DNA Repair
https://www.readbyqxmd.com/read/28189416/repair-of-oxidative-dna-damage-in-saccharomyces-cerevisiae
#4
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...
January 28, 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
#5
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...
January 17, 2017: DNA Repair
https://www.readbyqxmd.com/read/28109743/regulation-of-human-pol%C3%AE-by-atm-mediated-phosphorylation-during-non-homologous-end-joining
#6
Guillermo Sastre-Moreno, John M Pryor, Marta Moreno-Oñate, Andrés M Herrero-Ruiz, Felipe Cortés-Ledesma, Luis Blanco, Dale A Ramsden, Jose F Ruiz
DNA double strand breaks (DSBs) trigger a variety of cellular signaling processes, collectively termed the DNA-damage response (DDR), that are primarily regulated by protein kinase ataxia-telangiectasia mutated (ATM). Among DDR activated processes, the repair of DSBs by non-homologous end joining (NHEJ) is essential. The proper coordination of NHEJ factors is mainly achieved through phosphorylation by an ATM-related kinase, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the molecular basis for this regulation has yet to be fully elucidated...
January 17, 2017: DNA Repair
https://www.readbyqxmd.com/read/28108275/benzofuran-2-acetic-ester-derivatives-induce-apoptosis-in-breast-cancer-cells-by-upregulating-p21-cip-waf1-gene-expression-in-p53-independent-manner
#7
Cinzia Giordano, Daniela Rovito, Ines Barone, Raffaella Mancuso, Daniela Bonofiglio, Francesca Giordano, Stefania Catalano, Bartolo Gabriele, Sebastiano Andò
Breast cancer is the most common malignancy and the leading cause of cancer-related death in women worldwide. High toxicity of used chemotherapeutics and resistance of cancer cells to treatments are a driving force for searching the new drug candidates for breast cancer therapy. In this study, we tested the antiproliferative effects of a series of benzofuran-2-acetic methyl ester derivatives, synthesized by a palladium-catalyzed carbonylative heterocyclization approach, on breast cancer cells. We observed that benzofuran compounds bearing a phenyl or tert-butyl substituent α to the methoxycarbonyl group significantly inhibited anchorage-dependent and -independent cell growth, and induced G0/G1 cell cycle arrest in human estrogen receptor alpha positive (MCF-7 and T47D) and in triple negative MDA-MB-231 breast cancer cells, without affecting growth of MCF-10A normal breast epithelial cells...
January 15, 2017: DNA Repair
https://www.readbyqxmd.com/read/28110804/differential-role-of-base-excision-repair-proteins-in-mediating-cisplatin-cytotoxicity
#8
Akshada Sawant, Ashley M Floyd, Mohan Dangeti, Wen Lei, Robert W Sobol, Steve M Patrick
Interstrand crosslinks (ICLs) are covalent lesions formed by cisplatin. The mechanism for the processing and removal of ICLs by DNA repair proteins involves nucleotide excision repair (NER), homologous recombination (HR) and fanconi anemia (FA) pathways. In this report, we monitored the processing of a flanking uracil adjacent to a cisplatin ICL by the proteins involved in the base excision repair (BER) pathway. Using a combination of extracts, purified proteins, inhibitors, functional assays and cell culture studies, we determined the specific BER proteins required for processing a DNA substrate with a uracil adjacent to a cisplatin ICL...
January 11, 2017: DNA Repair
https://www.readbyqxmd.com/read/28108274/the-crosstalk-between-wnt-%C3%AE-catenin-signaling-pathway-with-dna-damage-response-and-oxidative-stress-implications-in-cancer-therapy
#9
REVIEW
Ansar Karimaian, Maryam Majidinia, Hossein Bannazadeh Baghi, Bahman Yousefi
DNA repair is essential for maintaining genomic integrity in cells. The dependence of cancer cell survival on proper DNA repair provides an opportunity to treat defective tumors by DNA damaging agents. Not only Wnt signaling has important functions in controlling gene expression, as well as cell polarity, adhesion and behavior, it also highly interacts with DNA damage response (DDR) in different levels. Furthermore, oxidative stress, which is responsible for majority of DNA lesions, affects Wnt signaling in different ways...
January 11, 2017: DNA Repair
https://www.readbyqxmd.com/read/28034630/defect-of-fe-s-cluster-binding-by-dna-polymerase-%C3%AE-in-yeast-suppresses-uv-induced-mutagenesis-but-enhances-dna-polymerase-%C3%AE-dependent-spontaneous-mutagenesis
#10
E I Stepchenkova, E R Tarakhovskaya, H M Siebler, Y I Pavlov
Eukaryotic genomes are duplicated by a complex machinery, utilizing high fidelity replicative B-family DNA polymerases (pols) α, δ and ε. Specialized error-prone pol ζ, the fourth B-family member, is recruited when DNA synthesis by the accurate trio is impeded by replication stress or DNA damage. The damage tolerance mechanism dependent on pol ζ prevents DNA/genome instability and cell death at the expense of increased mutation rates. The pol switches occurring during this specialized replication are not fully understood...
December 9, 2016: DNA Repair
https://www.readbyqxmd.com/read/27964836/non-heme-dioxygenases-in-tumor-hypoxia-they-re-all-bound-with-the-same-fate
#11
REVIEW
Roy Anindya
Tumor tissues are known to harbor hypoxic areas. The hypoxic microenvironment promotes angiogenesis. Hypoxic tumor cells also manifest genome instability. DNA damage repair pathways, such as double-strand break repair, mismatch repair and base excision repair are known to be altered during hypoxia. This review is focused on the non-heme Fe(II) and 2-oxoglutarate-dependent dioxygenases which are involved in repair of DNA alkylation adducts. Activities of these DNA repair enzymes are completely oxygen-dependent and little information is available about inhibition of these enzymes during hypoxia...
December 5, 2016: DNA Repair
https://www.readbyqxmd.com/read/28089177/cell-cycle-dependent-positive-and-negative-functions-of-fun30-chromatin-remodeler-in-dna-damage-response
#12
Jasmine Siler, Bowen Xia, Carina Wong, Morgan Kath, Xin Bi
The evolutionally conserved Fun30 chromatin remodeler in Saccharomyces cerevisiae has been shown to contribute to cellular resistance to genotoxic stress inflicted by camptothecin (CPT), methyl methanesulfonate (MMS) and hydroxyurea (HU). Fun30 aids in extensive DNA resection of DNA double stranded break (DSB) ends, which is thought to underlie its role in CPT-resistance. How Fun30 promotes MMS- or HU-resistance has not been resolved. Interestingly, we have recently found Fun30 to also play a negative role in cellular tolerance to MMS and HU in the absence of the Rad5-dependent DNA damage tolerance pathway...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28087249/nick-initiated-homologous-recombination-protecting-the-genome-one-strand-at-a-time
#13
REVIEW
Lianne E M Vriend, Przemek M Krawczyk
Homologous recombination (HR) is an essential, widely conserved mechanism that utilizes a template for accurate repair of DNA breaks. Some early HR models, developed over five decades ago, anticipated single-strand breaks (nicks) as initiating lesions. Subsequent studies favored a more double-strand break (DSB)-centered view of HR initiation and at present this pathway is primarily considered to be associated with DSB repair. However, mounting evidence suggests that nicks can indeed initiate HR directly, without first being converted to DSBs...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28082021/somatic-hypermutation-of-immunoglobulin-genes-in-rad18-knockout-mice
#14
Takeyuki Shimizu, Satoshi Tateishi, Yuki Tanoue, Takachika Azuma, Haruo Ohmori
Somatic hypermutation (SHM) of immunoglobulin (Ig) genes is triggered by the activity of activation-induced cytidine deaminase (AID). AID induces DNA lesions in variable regions of Ig genes, and error-prone DNA repair mechanisms initiated in response to these lesions introduce the mutations that characterize SHM. Error-prone DNA repair in SHM is proposed to be mediated by low-fidelity DNA polymerases such as those that mediate trans-lesion synthesis (TLS); however, the mechanism by which these enzymes are recruited to AID-induced lesions remains unclear...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28077248/alternative-splicing-at-exon-2-results-in-the-loss-of-the-catalytic-activity-of-mouse-dna-polymerase-iota-in-vitro
#15
Konstantin Y Kazachenko, Nataliya A Miropolskaya, Leonid V Gening, Vyacheslav Z Tarantul, Alena V Makarova
Y-family DNA polymerase iota (Pol ι) possesses both DNA polymerase and dRP lyase activities and was suggested to be involved in DNA translesion synthesis and base excision repair in mammals. The 129 strain of mice and its derivatives have a natural nonsense codon mutation in the second exon of the Pol ι gene resulting in truncation of the Pol ι protein. These mice were widely used as a Pol ι-null model for in vivo studies of the Pol ι function. However whether 129-derived strains of mice are fully deficient in the Pol ι functions was a subject of discussion since Pol ι mRNA undergoes alternative splicing at exon 2...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28077247/mouse-dna-polymerase-%C3%AE-lacking-the-forty-two-amino-acids-encoded-by-exon-2-is-catalytically-inactive-in-vitro
#16
Ekaterina G Frank, John P McDonald, Wei Yang, Roger Woodgate
In 2003, we reported that 129-derived strains of mice carry a naturally occurring nonsense mutation at codon 27 of the Poli gene that would produce a polι peptide of just 26 amino acids, rather then the full-length 717 amino acid wild-type polymerase. In support of the genomic analysis, no polι protein was detected in testes extracts from 129X1/SvJmice, where wild-type polι is normally highly expressed. The early truncation in polι occurs before any structural domains of the polymerase are synthesized and as a consequence, we reasoned that 129-derived strains of mice should be considered as functionally defective in polι activity...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28073635/pcna-dependent-cellular-activities-tolerate-dramatic-perturbations-in-pcna-client-interactions
#17
Rosemary H C Wilson, Antonio J Biasutto, Lihao Wang, Roman Fischer, Emma L Baple, Andrew H Crosby, Erika J Mancini, Catherine M Green
Proliferating cell nuclear antigen (PCNA) is an essential cofactor for DNA replication and repair, recruiting multiple proteins to their sites of action. We examined the effects of the PCNA(S228I) mutation that causes PCNA-associated DNA repair disorder (PARD). Cells from individuals affected by PARD are sensitive to the PCNA inhibitors T3 and T2AA, showing that the S228I mutation has consequences for undamaged cells. Analysis of the binding between PCNA and PCNA-interacting proteins (PIPs) shows that the S228I change dramatically impairs the majority of these interactions, including that of Cdt1, DNMT1, PolD3(p66) and PolD4(p12)...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28065385/processing-of-the-abasic-sites-clustered-with-the-benzo-a-pyrene-adducts-by-the-base-excision-repair-enzymes
#18
Lidia V Starostenko, Nadejda I Rechkunova, Natalia A Lebedeva, Alexander A Lomzov, Vladimir V Koval, Olga I Lavrik
The major enzyme in eukaryotic cells that catalyzes the cleavage of apurinic/apyrimidinic (AP or abasic) sites is AP endonuclease 1 (APE1) that cleaves the phosphodiester bond on the 5'-side of AP sites. We found that the efficiency of AP site cleavage by APE1 was affected by the benzo[a]pyrenyl-DNA adduct (BPDE-dG) in the opposite strand. AP sites directly opposite of the modified dG or shifted toward the 5' direction were hydrolyzed by APE1 with an efficiency moderately lower than the AP site in the control DNA duplex, whereas AP sites shifted toward the 3' direction were hydrolyzed significantly less efficiently...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28063664/hesperetin-etoposide-combinations-induce-cytotoxicity-in-u2os-cells-implications-on-therapeutic-developments-for-osteosarcoma
#19
Laura Coutinho, Helena Oliveira, Ana Rita Pacheco, Luis Almeida, Francisco Pimentel, Conceição Santos, José Miguel P Ferreira de Oliveira
Osteosarcoma chemotherapy has improved survival rates, however, chemoresistance and drug toxicity still limit therapy. Drug combinations may overcome these limitations by allowing fewer chemoresistant cells to survive. The aim of this study was to evaluate the cytotoxic potential of hesperetin to osteosarcoma and to analyze the cell cycle effects of combinations of hesperetin with chemotherapeutic agents. For this, the U2OS human osteosarcoma cell line was exposed to hesperetin or hesperetin combined with etoposide or doxorubicin in defined proportions...
February 2017: DNA Repair
https://www.readbyqxmd.com/read/28017527/dna-damage-repair-monitoring-and-epigenetic-dna-methylation-changes-in-seedlings-of-chernobyl-soybeans
#20
Mariyana Georgieva, Namik M Rashydov, Martin Hajduch
This pilot study was carried out to assess the effect of radio-contaminated Chernobyl environment on plant genome integrity 27 years after the accident. For this purpose, nuclei were isolated from root tips of the soybean seedlings harvested from plants grown in the Chernobyl area for seven generations. Neutral, neutral-alkaline, and methylation-sensitive comet assays were performed to evaluate the induction and repair of primary DNA damage and the epigenetic contribution to stress adaptation mechanisms. An increased level of single and double strand breaks in the radio-contaminated Chernobyl seedlings at the stage of primary root development was detected in comparison to the controls...
February 2017: DNA Repair
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