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nucleotide excision repair

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https://www.readbyqxmd.com/read/28212410/a-high-throughput-genetic-screen-identifies-previously-uncharacterized-borrelia-burgdorferi-genes-important-for-resistance-against-reactive-oxygen-and-nitrogen-species
#1
Meghan E Ramsey, Jenny A Hyde, Diana N Medina-Perez, Tao Lin, Lihui Gao, Maureen E Lundt, Xin Li, Steven J Norris, Jon T Skare, Linden T Hu
Borrelia burgdorferi, the causative agent of Lyme disease in humans, is exposed to reactive oxygen and nitrogen species (ROS and RNS) in both the tick vector and vertebrate reservoir hosts. B. burgdorferi contains a limited repertoire of canonical oxidative stress response genes, suggesting that novel gene functions may be important for protection of B. burgdorferi against ROS or RNS exposure. Here, we use transposon insertion sequencing (Tn-seq) to conduct an unbiased search for genes involved in resistance to nitric oxide, hydrogen peroxide, and tertiary-butyl hydroperoxide in vitro...
February 17, 2017: PLoS Pathogens
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
#2
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/28207808/autologous-hematopoietic-stem-cell-transplantation-in-lymphoma-patients-is-associated-with-a-decrease-in-the-double-strand-break-repair-capacity-of-peripheral-blood-lymphocytes
#3
Sandrine Lacoste, Smita Bhatia, Yanjun Chen, Ravi Bhatia, Timothy R O'Connor
Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28207748/nucleotide-pools-dictate-the-identity-and-frequency-of-ribonucleotide-incorporation-in-mitochondrial-dna
#4
Anna-Karin Berglund, Clara Navarrete, Martin K M Engqvist, Emily Hoberg, Zsolt Szilagyi, Robert W Taylor, Claes M Gustafsson, Maria Falkenberg, Anders R Clausen
Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides...
February 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28202049/costs-and-benefits-of-natural-transformation-in-acinetobacter-baylyi
#5
Nils Hülter, Vidar Sørum, Kristina Borch-Pedersen, Mikkel M Liljegren, Ane L G Utnes, Raul Primicerio, Klaus Harms, Pål J Johnsen
BACKGROUND: Natural transformation enables acquisition of adaptive traits and drives genome evolution in prokaryotes. Yet, the selective forces responsible for the evolution and maintenance of natural transformation remain elusive since taken-up DNA has also been hypothesized to provide benefits such as nutrients or templates for DNA repair to individual cells. RESULTS: We investigated the immediate effects of DNA uptake and recombination on the naturally competent bacterium Acinetobacter baylyi in both benign and genotoxic conditions...
February 15, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28199404/loss-of-genes-related-to-nucleotide-excision-repair-ner-and-implications-for-reductive-genome-evolution-in-symbionts-of-deep-sea-vesicomyid-clams
#6
Shigeru Shimamura, Takashi Kaneko, Genki Ozawa, Mamiko Nishino Matsumoto, Takeru Koshiishi, Yoshihiro Takaki, Chiaki Kato, Ken Takai, Takao Yoshida, Katsunori Fujikura, James P Barry, Tadashi Maruyama
Intracellular thioautotrophic symbionts of deep-sea vesicomyid clams lack some DNA repair genes and are thought to be undergoing reductive genome evolution (RGE). In this study, we addressed two questions, 1) how these symbionts lost their DNA repair genes and 2) how such losses affect RGE. For the first question, we examined genes associated with nucleotide excision repair (NER; uvrA, uvrB, uvrC, uvrD, uvrD paralog [uvrDp] and mfd) in 12 symbionts of vesicomyid clams belonging to two clades (5 clade I and 7 clade II symbionts)...
2017: PloS One
https://www.readbyqxmd.com/read/28192636/paracrine-regulation-of-melanocyte-genomic-stability-a-focus-on-nucleotide-excision-repair
#7
REVIEW
Stuart Gordon Jarrett, Katharine Marie Carter, John August D'Orazio
UV radiation is a major environmental risk factor for the development of melanoma by causing DNA damage and mutations. Resistance to UV damage is largely determined by the capacity of melanocytes to respond to UV injury by repairing mutagenic photolesions. The nucleotide excision repair (NER) pathway is the major mechanism by which cells correct UV photodamage. This multi-step process involves the basic steps of damage recognition, isolation, localized strand unwinding, assembly of a repair complex, excision of the damage-containing strand 3' and 5' to the photolesion, synthesis of a sequence-appropriate replacement strand and finally ligation to restore continuity of genomic DNA...
February 13, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28192521/acquired-resistance-to-oxaliplatin-is-not-directly-associated-with-increased-resistance-to-dna-damage-in-sk-n-asroxali4000-a-newly-established-oxaliplatin-resistant-sub-line-of-the-neuroblastoma-cell-line-sk-n-as
#8
Emily Saintas, Liam Abrahams, Gulshan T Ahmad, Anu-Oluwa M Ajakaiye, Abdulaziz S H A M AlHumaidi, Candice Ashmore-Harris, Iain Clark, Usha K Dura, Carine N Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M U Schöler, Husne Timur, Maxwell D C Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E Hogwood, Pamela E Lithgow, Michelle Rowe, Lyto Yiangou, Florian Rothweiler, Jindrich Cinatl, Richard Zehner, Anthony J Baines, Michelle D Garrett, Campbell W Gourlay, Darren K Griffin, William J Gullick, Emma Hargreaves, Mark J Howard, Daniel R Lloyd, Jeremy S Rossman, C Mark Smales, Anastasios D Tsaousis, Tobias von der Haar, Mark N Wass, Martin Michaelis
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin...
2017: PloS One
https://www.readbyqxmd.com/read/28191901/increasing-the-genome-targeting-scope-and-precision-of-base-editing-with-engineered-cas9-cytidine-deaminase-fusions
#9
Y Bill Kim, Alexis C Komor, Jonathan M Levy, Michael S Packer, Kevin T Zhao, David R Liu
Base editing induces single-nucleotide changes in the DNA of living cells using a fusion protein containing a catalytically defective Streptococcus pyogenes Cas9, a cytidine deaminase, and an inhibitor of base excision repair. This genome editing approach has the advantage that it does not require formation of double-stranded DNA breaks or provision of a donor DNA template. Here we report the development of five C to T (or G to A) base editors that use natural and engineered Cas9 variants with different protospacer-adjacent motif (PAM) specificities to expand the number of sites that can be targeted by base editing 2...
February 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28185850/an-improved-method-for-the-detection-of-nucleotide-excision-repair-factors-at-local-uv-dna-damage-sites
#10
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/28159786/bacteriophage-%C3%AE-m1-of-pectobacterium-evolves-to-escape-two-bifunctional-type-iii-toxin-antitoxin-and-abortive-infection-systems-through-mutations-in-a-single-viral-gene
#11
Tim R Blower, Ray Chai, Rita Przybilski, Shahzad Chindhy, Xinzhe Fang, Samuel E Kidman, Hui Tan, Ben F Luisi, Peter C Fineran, George P C Salmond
: Some bacteria, when infected by their viral parasites (bacteriophages), undergo a suicidal response that also terminates productive viral replication (abortive infection; Abi). This response can be viewed as an altruistic act protecting the uninfected bacterial clonal population. Abortive infection can occur through the action of Type III protein-RNA toxin-antitoxin (TA) systems, such as ToxINPa from the phytopathogen, Pectobacterium atrosepticum Rare spontaneous mutants evolved in the generalized transducing phage, ΦM1, which escaped ToxINPa-mediated abortive infection in P...
February 3, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28154196/dna-repair-in-drosophila-mutagens-models-and-missing-genes
#12
Jeff Sekelsky
The numerous processes that damage DNA are counterbalanced by a complex network of repair pathways that, collectively, can mend diverse types of damage. Insights into these pathways have come from studies in many different organisms, including Drosophila melanogaster Indeed, the first ideas about chromosome and gene repair grew out of Drosophila research on the properties of mutations produced by ionizing radiation and mustard gas. Numerous methods have been developed to take advantage of Drosophila genetic tools to elucidate repair processes in whole animals, organs, tissues, and cells...
February 2017: Genetics
https://www.readbyqxmd.com/read/28143930/oxidative-dna-damage-is-epigenetic-by-regulating-gene-transcription-via-base-excision-repair
#13
Aaron M Fleming, Yun Ding, Cynthia J Burrows
Reactive oxygen species (ROS) have emerged as important cellular-signaling agents for cellular survival. Herein, we demonstrate that ROS-mediated oxidation of DNA to yield 8-oxo-7,8-dihydroguanine (OG) in gene promoters is a signaling agent for gene activation. Enhanced gene expression occurs when OG is formed in guanine-rich, potential G-quadruplex-forming sequences (PQS) in promoter-coding strands, initiating base excision repair (BER) by 8-oxoguanine DNA glycosylase (OGG1), yielding an abasic site (AP). The AP enables melting of the duplex to unmask the PQS, adopting a G-quadruplex fold in which apurinic/apyrimidinic endonuclease 1 (APE1) binds, but inefficiently cleaves, the AP for activation of vascular endothelial growth factor (VEGF) or endonuclease III-like protein 1 (NTHL1) genes...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28132856/nadph-oxidase-1-plays-a-key-role-in-keratinocyte-responses-to-ultraviolet-radiation-and-uvb-induced-skin-carcinogenesis
#14
Houssam Raad, Martin Serrano-Sanchez, Ghida Harfouche, Walid Mahfouf, Doriane Bortolotto, Vanessa Bergeron, Zeinab Kasraian, Lea Dousset, Mohsen Hosseini, Alain Taieb, Hamid Reza Rezvani
The NADPH oxidase (NOX) family enzymes are involved in several physiological functions. However, their roles in keratinocyte responses to ultraviolet (UV) radiation have not been clearly elucidated. This study demonstrates that, among other NOX family members, UVB irradiation results in a biphasic activation of NOX1 that plays a critical role in defining keratinocyte fate through the modulation of the DNA damage response (DDR) network. Indeed, suppression of both bursts of UVB-induced NOX1 activation by using a specific peptide inhibitor of NOX1 (InhNOX1) is associated with increased nucleotide excision repair (NER) efficiency and reduction of apoptosis, which is finally translated into decreased photocarcinogenesis...
January 26, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28130555/xpf-knockout-via-crispr-cas9-reveals-that-ercc1-is-retained-in-the-cytoplasm-without-its-heterodimer-partner-xpf
#15
Janin Lehmann, Christina Seebode, Sabine Smolorz, Steffen Schubert, Steffen Emmert
The XPF/ERCC1 heterodimeric complex is essentially involved in nucleotide excision repair (NER), interstrand crosslink (ICL), and double-strand break repair. Defects in XPF lead to severe diseases like xeroderma pigmentosum (XP). Up until now, XP-F patient cells have been utilized for functional analyses. Due to the multiple roles of the XPF/ERCC1 complex, these patient cells retain at least one full-length allele and residual repair capabilities. Despite the essential function of the XPF/ERCC1 complex for the human organism, we successfully generated a viable immortalised human XPF knockout cell line with complete loss of XPF using the CRISPR/Cas9 technique in fetal lung fibroblasts (MRC5Vi cells)...
January 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28123580/effects-of-physical-activity-on-systemic-oxidative-dna-status-in-breast-cancer-survivors
#16
Barbara Tomasello, Giuseppe Antonio Malfa, Angela Strazzanti, Santi Gangi, Claudia Di Giacomo, Francesco Basile, Marcella Renis
Physical activity offers a paradoxical hormetic effect and a health benefit to cancer survivors; however, the biochemical mechanisms have not been entirely elucidated. Despite the well-documented evidence implicating oxidative stress in breast cancer, the association between health benefits and redox status has not been investigated in survivors who participate in dragon boating. The present study investigated the plasmatic systemic oxidative status (SOS) in breast cancer survivors involved in two distinct physical training exercises...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28120709/dna-damaging-anticancer-drugs-a-perspective-for-dna-repair-oriented-therapy
#17
Janusz Blasiak
DNA-damaging drugs in cancer present two main problems: therapeutic resistance and side effects and both can associate with DNA repair, which can be targeted in cancer therapy. Bleomycin (BLM) induces complex DNA damages, including strand breaks, base loss and 3'-phosphoglycolate (3'PG) residues repaired by several pathways, but 3'PGs must be processed to the 3'-OH ends, usually by tyrosyl-DNA phosphodiesterase 1 (Tdp1). Therefore, targeting Tdp1 can improve anticancer therapy with BLM. Mitomycin C (MMC) produces a variety of adducts with DNA, including inter-strand cross-links (ICLs) and Xeroderma pigmentosum (XP) proteins, including XPG, XPE and XPF can be crucial for the initial stage of ICL repair, so they can be targeted by inhibitors to increase toxicity of MMC in cancer cells...
January 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28120472/optical-control-of-dna-helicase-function-through-genetic-code-expansion
#18
Ji Luo, Muwen Kong, Lili Liu, Subhas Samanta, Bennett Van Houten, Alexander Deiters
Nucleotide excision repair (NER) is a general DNA repair mechanism that is capable of removing a wide variety of DNA lesions induced by physical or chemical insults. UvrD, a member of the helicase SF1 superfamily, plays an essential role in bacterial NER by unwinding the duplex DNA in the 3' to 5' direction to displace the lesion-containing strand. In order to achieve conditional control over NER, we generated a light-activated DNA helicase. This was achieved through a site-specific incorporation of a genetically encoded hydroxycoumarin lysine at a crucial position in the ATP-binding pocket of UvrD...
January 25, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28120344/dna-base-excision-repair-genetic-risk-scores-oxidative-balance-and-incident-sporadic-colorectal-adenoma
#19
Tengteng Wang, Michael Goodman, Yan V Sun, Bharat Thyagarajan, Myron Gross, Roberd M Bostick
Associations of individual base excision repair (BER) genotypes with colorectal adenoma risk are unclear, but likely modest. However, genetic risk scores (GRS) that aggregate information from multiple genetic variants might be useful for assessing genetic predisposition to colorectal adenoma. We analyzed data pooled from three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 488 cases, 604 controls) that collected blood for genotyping and extensive dietary and other data...
January 24, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28116145/overexpression-of-pcna-attenuates-oxidative-stress-caused-delay-of-gap-filling-during-repair-of-uv-induced-dna-damage
#20
Yi-Chih Tsai, Yi-Hsiang Wang, Yin-Chang Liu
UVC irradiation-caused DNA lesions are repaired in mammalian cells solely by nucleotide excision repair (NER), which consists of sequential events including initial damage recognition, dual incision of damage site, gap-filling, and ligation. We have previously shown that gap-filling during the repair of UV-induced DNA lesions may be delayed by a subsequent treatment of oxidants or prooxidants such as hydrogen peroxide, flavonoids, and colcemid. We considered the delay as a result of competition for limiting protein/enzyme factor(s) during repair synthesis between NER and base excision repair (BER) induced by the oxidative chemicals...
2017: Journal of Nucleic Acids
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