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https://www.readbyqxmd.com/read/28439991/melatonin-a-pleiotropic-molecule-that-modulates-dna-damage-response-and-repair-pathways
#1
REVIEW
Maryam Majidinia, Alireza Sadeghpour, Saeed Mehrzadi, Russel J Reiter, Nasrin Khatami, Bahman Yousefi
DNA repair is responsible for maintaining the integrity of the genome. Perturbations in the DNA repair pathways have been identified in several human cancers. Thus, compounds targeting DNA damage response (DDR) hold great promise in cancer therapy. A great deal of effort, in pursuit of new anticancer drugs, has been devoted to understanding the basic mechanisms and functions of the cellular DNA repair machinery. Melatonin, a widely-produced indoleamine in all organisms is associated with a reduced risk of cancer and has multiple regulatory roles on the different aspects of the DDR and DNA repair...
April 25, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28431926/multiple-repair-pathways-mediate-cellular-tolerance-to-resveratrol-induced-dna-damage
#2
Ying Liu, Xiaohua Wu, Xiaoqing Hu, Ziyuan Chen, Hao Liu, Shunichi Takeda, Yong Qing
Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects...
April 19, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28415784/misregulation-of-dna-damage-repair-pathways-in-hpv-positive-head-and-neck-squamous-cell-carcinoma-contributes-to-cellular-radiosensitivity
#3
Catherine M Nickson, Parisa Moori, Rachel J Carter, Carlos P Rubbi, Jason L Parsons
Patients with human papillomavirus type 16 (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCC) display increased sensitivity to radiotherapy and improved survival rates in comparison to HPV-negative forms of the disease. However the cellular mechanisms responsible for this characteristic difference are unclear. Here, we have investigated the contribution of DNA damage repair pathways to the in vitro radiosensitivity of OPSCC cell lines. We demonstrate that two HPV-positive OPSCC cells are indeed more radiosensitive than two HPV-negative OPSCC cells, which correlates with reduced efficiency for the repair of ionising radiation (IR)-induced DNA double strand breaks (DSB)...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28391506/inactivation-of-genes-involved-in-base-excision-repair-of-corynebacterium-glutamicum-and-survival-of-the-mutants-in-presence-of-various-mutagens
#4
Fabiola Kautzmann, Josef Altenbuchner
Base Excision Repair (BER) is considered as the most active DNA repair pathway in vivo, which is initiated by recognition of the nucleotide lesions and excision of the damaged DNA base. The genome of Corynebacterium glutamicum ATCC 13032 contains various DNA glycosylases encoding genes (ung, fpg/mutM, tagI, alkA, mutY), two AP-endonuclease encoding genes (nei and nth) and an exonuclease encoding gene xth. To investigate the role of these genes during DNA repair in C. glutamicum, mutants with deletions of one or more genes in BER pathway were created...
April 8, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28373211/a-new-sub-pathway-of-long-patch-base-excision-repair-involving-5-gap-formation
#5
Jordan Woodrick, Suhani Gupta, Sharon Camacho, Swetha Parvathaneni, Sujata Choudhury, Amrita Cheema, Yi Bai, Pooja Khatkar, Hayriye Verda Erkizan, Furqan Sami, Yan Su, Orlando D Schärer, Sudha Sharma, Rabindra Roy
Base excision repair (BER) is one of the most frequently used cellular DNA repair mechanisms and modulates many human pathophysiological conditions related to DNA damage. Through live cell and in vitro reconstitution experiments, we have discovered a major sub-pathway of conventional long-patch BER that involves formation of a 9-nucleotide gap 5' to the lesion. This new sub-pathway is mediated by RECQ1 DNA helicase and ERCC1-XPF endonuclease in cooperation with PARP1 poly(ADP-ribose) polymerase and RPA The novel gap formation step is employed during repair of a variety of DNA lesions, including oxidative and alkylation damage...
April 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28371273/fen1-promotes-tumor-progression-and-confers-cisplatin-resistance-in-non-small-cell-lung-cancer
#6
Lingfeng He, Libo Luo, Hong Zhu, Huan Yang, Yilan Zhang, Huan Wu, Hongfang Sun, Feng Jiang, Chandra Sekhar Kathera, Lingjie Liu, Ziheng Zhuang, Haoyan Chen, Feiyan Pan, Zhigang Hu, Jing Zhang, Zhigang Guo
Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair (BER) pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells...
March 29, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28357058/how-are-base-excision-dna-repair-pathways-deployed-in-vivo
#7
REVIEW
Upasna Thapar, Bruce Demple
Since the discovery of the base excision repair (BER) system for DNA more than 40 years ago, new branches of the pathway have been revealed at the biochemical level by in vitro studies. Largely for technical reasons, however, the confirmation of these subpathways in vivo has been elusive. We review methods that have been used to explore BER in mammalian cells, indicate where there are important knowledge gaps to fill, and suggest a way to address them.
2017: F1000Research
https://www.readbyqxmd.com/read/28351647/apobec3b-cytidine-deaminase-targets-the-non-transcribed-strand-of-trna-genes-in-yeast
#8
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/28333944/mechanisms-of-glycosylase-induced-genomic-instability
#9
Daniel E Eyler, Kylie A Burnham, Thomas E Wilson, Patrick J O'Brien
Human alkyladenine DNA glycosylase (AAG) initiates base excision repair (BER) to guard against mutations by excising alkylated and deaminated purines. Counterintuitively, increased expression of AAG has been implicated in increased rates of spontaneous mutation in microsatellite repeats. This microsatellite mutator phenotype is consistent with a model in which AAG excises bulged (unpaired) bases, altering repeat length. To directly test the role of base excision in AAG-induced mutagenesis, we conducted mutation accumulation experiments in yeast overexpressing different variants of AAG and detected mutations via high-depth genome resequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28315507/polymorphisms-and-mutations-in-gstp1-rad51-xrcc1-and-xrcc3-genes-in-breast-cancer-patients
#10
Mazhar Salim Al Zoubi, Katia Zavaglia, Chiara Mazanti, Mohammad Al Hamad, Khalid Al Batayneh, Alaa A A Aljabali, Generoso Bevilacqua
BACKGROUND: Genotoxic factors, including ionizing radiation and oxidative stress, are associated with genomic instability and development of breast cancer (BC). The homologous recombination DNA repair (HRR) pathway, base excision repair (BER) mechanism, and antioxidative enzymes are required as defense mechanisms against these DNA damaging agents. GSTP1, XRCC1, XRCC3 and RAD51 proteins are essential components of antioxidation, BER and HRR of DNA, respectively. Deficiencies in BER, HRR and antioxidation pathways are involved in the progression of cancer...
March 6, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28267381/dynamics-of-5-carboxylcytosine-during-hepatic-differentiation-potential-general-role-for-active-demethylation-by-dna-repair-in-lineage-specification
#11
Lara C Lewis, Peggy Cho Kiu Lo, Jeremy M Foster, Nan Dai, Ivan R Corrêa, Paulina M Durczak, Gary Duncan, Ashley Ramsawhook, Guruprasad Padur Aithal, Chris Denning, Nicholas R F Hannan, Alexey Ruzov
Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operational in this system; however, it is still unknown if TDG/BER-dependent demethylation is used during other types of cellular differentiation...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28266569/ogg1-dna-interactions-facilitate-nf-%C3%AE%C2%BAb-binding-to-dna-targets
#12
Lang Pan, Wenjing Hao, Xu Zheng, Xianlu Zeng, Adeel Ahmed Abbasi, Istvan Boldogh, Xueqing Ba
DNA repair protein counteracting oxidative promoter lesions may modulate gene expression. Oxidative DNA bases modified by reactive oxygen species (ROS), primarily as 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair (BER) pathway. Because cellular response to oxidative challenge is accompanied by DNA damage repair, we tested whether the repair by OGG1 is compatible with transcription factor binding and gene expression. We performed electrophoretic mobility shift assay (EMSA) using wild-type sequence deriving from Cxcl2 gene promoter and the same sequence bearing a single synthetic 8-oxoG at defined 5' or 3' guanine in runs of guanines to mimic oxidative effects...
March 7, 2017: Scientific Reports
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
#13
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/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
#14
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/28242328/mitochondrial-transcription-factor-a-tfam-rs1937-and-ap-endonuclease-1-ape1-rs1130409-alleles-are-associated-with-reduced-cognitive-performance
#15
Meryl S Lillenes, Mari Støen, Clara-Cecilie Günther, Per Selnes, Vidar T V Stenset, Thomas Espeseth, Ivar Reinvang, Tormod Fladby, Tone Tønjum
Mitochondrial dysfunction and DNA damage is intimately connected to ageing and neurodegeneration, including Alzheimer's disease (AD). A particular culprit in this context is oxidative stress, which is a result of increased reactive oxygen species (ROS) due to hyperactive or dysfunctional mitochondria and/or reduced DNA repair capacity. Base excision repair (BER) is the major pathway for repairing oxidative damage events in chromosomal and mitochondrial DNA. Defects in BER have been detected in ageing and neurodegeneration...
February 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28199214/base-excision-repair-of-oxidative-dna-damage-from-mechanism-to-disease
#16
Amy M Whitaker, Matthew A Schaich, Mallory S Smith, Tony S Flynn, Bret D Freudenthal
Reactive oxygen species continuously assault the structure of DNA resulting in oxidation and fragmentation of the nucleobases. Both oxidative DNA damage itself and its repair mediate the progression of many prevalent human maladies. The major pathway tasked with removal of oxidative DNA damage, and hence maintaining genomic integrity, is base excision repair (BER). The aphorism that structure often dictates function has proven true, as numerous recent structural biology studies have aided in clarifying the molecular mechanisms used by key BER enzymes during the repair of damaged DNA...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28181292/tumor-associated-ape1-variant-exhibits-reduced-complementation-efficiency-but-does-not-promote-cancer-cell-phenotypes
#17
Jennifer L Illuzzi, Daniel R McNeill, Paul Bastian, Boris Brenerman, Robert Wersto, Helen R Russell, Fred Bunz, Peter J McKinnon, Kevin G Becker, David M Wilson
Base excision repair (BER) is the major pathway for coping with most forms of endogenous DNA damage, and defects in the process have been associated with carcinogenesis. Apurinic/apyrimidinic endonuclease 1 (APE1) is a central participant in BER, functioning as a critical endonuclease in the processing of noncoding abasic sites in DNA. Evidence has suggested that APE1 missense mutants, as well as altered expression or localization of the protein, can contribute to disease manifestation. We report herein that the tumor-associated APE1 variant, R237C, shows reduced complementation efficiency of the methyl methanesulfonate hypersensitivity and impaired cell growth exhibited by APE1-deficient mouse embryonic fibroblasts...
March 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28161249/inhibitors-of-nuclease-and-redox-activity-of-apurinic-apyrimidinic-endonuclease-1-redox-effector-factor-1-ape1-ref-1
#18
REVIEW
Sergey S Laev, Nariman F Salakhutdinov, Olga I Lavrik
Human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein which is essential in the base excision repair (BER) pathway of DNA lesions caused by oxidation and alkylation. This protein hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety or activates the DNA-binding activity of certain transcription factors through its redox function. Studies have indicated a role for APE1/Ref-1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs...
January 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28129601/pluripotent-cells-display-enhanced-resistance-to-mutagenesis
#19
Daniel J Cooper, I-Chung Chen, Christine Hernandez, Yufeng Wang, Christi A Walter, John R McCarrey
Pluripotent cells have been reported to exhibit lower frequencies of point mutations and higher levels of DNA repair than differentiated cells. This predicts that pluripotent cells are less susceptible to mutagenic exposures than differentiated cells. To test this prediction, we used a lacI mutation-reporter transgene system to assess the frequency of point mutations in multiple lines of mouse pluripotent embryonic stem cells and induced pluripotent cells, as well as in multiple lines of differentiated fibroblast cells, before and after exposure to a moderate dose of the mutagen, methyl methanesulfonate...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28129013/oxidative-dna-damage-and-reduced-expression-of-dna-repair-genes-role-in-primary-open-angle-glaucoma-poag
#20
Kuldeep Mohanty, Rima Dada, Tanuj Dada
BACKGROUND: Controversy exists regarding the role of oxidative DNA damage and DNA repair in primary open angle glaucoma (POAG). We performed a case control study to test the hypothesis that oxidative DNA damage and base excision repair (BER) genes PARP1 and OGG1 are involved in POAG pathogenesis. MATERIALS AND METHODS: The study included 116 POAG patients and 116 cataract patients as controls. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured by ELISA...
January 27, 2017: Ophthalmic Genetics
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