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https://www.readbyqxmd.com/read/28315507/polymorphisms-and-mutations-in-gstp1-rad51-xrcc1-and-xrcc3-genes-in-breast-cancer-patients
#1
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
#2
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 operative in this system; however, it is still unknown if TDG/BER-dependent demethylation is utilized during other types of cellular differentiation...
March 7, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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-%C3%A2
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28119421/dna-polymerase-%C3%AE-uses-its-lyase-domain-in-a-processive-search-for-dna-damage
#12
Michael J Howard, Yesenia Rodriguez, Samuel H Wilson
DNA polymerase (Pol) β maintains genome fidelity by catalyzing DNA synthesis and removal of a reactive DNA repair intermediate during base excision repair (BER). Situated within the middle of the BER pathway, Pol β must efficiently locate its substrates before damage is exacerbated. The mechanisms of damage search and location by Pol β are largely unknown, but are critical for understanding the fundamental features of the BER pathway. We developed a processive search assay to determine if Pol β has evolved a mechanism for efficient DNA damage location...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28110804/differential-role-of-base-excision-repair-proteins-in-mediating-cisplatin-cytotoxicity
#13
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...
March 2017: DNA Repair
https://www.readbyqxmd.com/read/28098985/hmgb1-stimulates-activity-of-polymerase-%C3%AE-on-nucleosome-substrates
#14
Angela Balliano, Fanfan Hao, Catherine Njeri, Lata Balakrishnan, Jeffrey J Hayes
The process of base excision repair (BER) recognizes and repairs small lesions or inappropriate bases on DNA through either a short-patch or long-patch pathway. The enzymes involved in BER have been well-characterized on DNA substrates, and, somewhat surprisingly, many of these enzymes, including several DNA glycosylases, AP endonuclease (APE), FEN1 endonuclease, and DNA ligases, have been shown to have activity on DNA substrates within nucleosomes. DNA polymerase β (Pol β), however, exhibits drastically reduced or no activity on nucleosomal DNA...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28087410/repair-of-8-oxog-a-mismatches-by-the-mutyh-glycosylase-mechanism-metals-and-medicine
#15
REVIEW
Douglas M Banda, Nicole N Nuñez, Michael A Burnside, Katie M Bradshaw, Sheila S David
Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome...
January 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28067485/honokiol-inhibits-dna-polymerases-%C3%AE-and-%C3%AE-and-increases-bleomycin-sensitivity-of-human-cancer-cells
#16
A S Prakasha Gowda, Zucai Suo, Thomas E Spratt
A major concept to sensitize cancer cells to DNA damaging agents is by inhibiting proteins in the DNA repair pathways. X-family DNA polymerases play critical roles in both base excision repair (BER) and nonhomologous end joining (NHEJ). In this study, we examined the effectiveness of honokiol to inhibit human DNA polymerase β (pol β), which is involved in BER, and DNA polymerase λ (pol λ), which is involved in NHEJ. Kinetic analysis with purified polymerases showed that honokiol inhibited DNA polymerase activity...
February 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28067232/oxidized-nucleotide-insertion-by-pol-%C3%AE-confounds-ligation-during-base-excision-repair
#17
Melike Çağlayan, Julie K Horton, Da-Peng Dai, Donna F Stefanick, Samuel H Wilson
Oxidative stress in cells can lead to accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized purine nucleotides can be inserted into DNA during replication and repair. The main pathway for correcting oxidized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase β (pol β) provides gap filling and tailoring functions. Here we report that the DNA ligation step of BER is compromised after pol β insertion of oxidized purine nucleotides into the BER intermediate in vitro...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28049757/smug2-dna-glycosylase-from-pedobacter-heparinus-as-a-new-subfamily-in-udg-superfamily
#18
Panjiao Pang, Ye Yang, Jing Li, Zhong Wang, Weiguo Cao, Wei Xie
Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are essential to maintain genome integrity, in which the base excision repair (BER) pathway plays a major role in the removal of base damage. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for excising the deaminated bases from DNA and generates apurinic/apyrimidinic (AP) sites. Using bioinformatics tools, we identified a family 3 SMUG1-like DNA glycoyslase from Pedobacter heparinus (named as Phe SMUG2), which display catalytic activities towards DNA containing uracil or hypoxanthine/xanthine...
January 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28040648/enhanced-degradation-of-azo-dye-by-a-stacked-microbial-fuel-cell-biofilm-electrode-reactor-coupled-system
#19
Xian Cao, Hui Wang, Xiao-Qi Li, Zhou Fang, Xian-Ning Li
In this study, a microbial fuel cell (MFC)-biofilm electrode reactor (BER) coupled system was established for degradation of the azo dye Reactive Brilliant Red X-3B. In this system, electrical energy generated by the MFC degrades the azo dye in the BER without the need for an external power supply, and the effluent from the BER was used as the inflow for the MFC, with further degradation. The results indicated that the X-3B removal efficiency was 29.87% higher using this coupled system than in a control group...
March 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28039326/proximity-to-agct-sequences-dictates-mmr-independent-versus-mmr-dependent-mechanisms-for-aid-induced-mutation-via-ung2
#20
Eddy Sanchai Thientosapol, George Sharbeen, K K Edwin Lau, Daniel Bosnjak, Timothy Durack, Igor Stevanovski, Wolfgang Weninger, Christopher J Jolly
AID deaminates C to U in either strand of Ig genes, exclusively producing C:G/G:C to T:A/A:T transition mutations if U is left unrepaired. Error-prone processing by UNG2 or mismatch repair diversifies mutation, predominantly at C:G or A:T base pairs, respectively. Here, we show that transversions at C:G base pairs occur by two distinct processing pathways that are dictated by sequence context. Within and near AGCT mutation hotspots, transversion mutation at C:G was driven by UNG2 without requirement for mismatch repair...
December 29, 2016: Nucleic Acids Research
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