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nucleotide excision repair

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https://www.readbyqxmd.com/read/28735741/apigenin-prevents-ultraviolet-b-radiation-induced-cyclobutane-pyrimidine-dimers-formation-in-human-dermal-fibroblasts
#1
S Mary Britto, D Shanthakumari, B Agilan, T Radhiga, G Kanimozhi, N Rajendra Prasad
Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm(2)); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM)...
September 2017: Mutation Research
https://www.readbyqxmd.com/read/28731186/let-7c-5p-inhibits-cell-proliferation-and-induces-cell-apoptosis-by-targeting-ercc6-in-breast-cancer
#2
Xiaonan Fu, Xuan Mao, Yuxiang Wang, Xianfeng Ding, Yongfeng Li
In this study, we found that let-7c-5p expression was clearly downregulated in breast cancer tissues compared with that of corresponding adjacent tissues. Furthermore, overexpression of let-7c-5p in MCF-7 breast cancer cells could significantly inhibit cell proliferation and induce cell apoptosis. The target genes of let-7c-5p were predicted by the way of bioinformatics, and validated by dual luciferase reporter assay and western blotting demonstrating that excision repair cross complementing 6 (ERCC6) gene was a direct target...
July 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28719581/phosphorylated-hbo1-at-uv-irradiated-sites-is-essential-for-nucleotide-excision-repair
#3
Hiroyuki Niida, Ryoichi Matsunuma, Ryo Horiguchi, Chiharu Uchida, Yuka Nakazawa, Akira Motegi, Koji Nishimoto, Satoshi Sakai, Tatsuya Ohhata, Kyoko Kitagawa, Shinichi Moriwaki, Hideo Nishitani, Ayako Ui, Tomoo Ogi, Masatoshi Kitagawa
HBO1, a histone acetyl transferase, is a co-activator of DNA pre-replication complex formation. We recently reported that HBO1 is phosphorylated by ATM and/or ATR and binds to DDB2 after ultraviolet irradiation. Here, we show that phosphorylated HBO1 at cyclobutane pyrimidine dimer (CPD) sites mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites. Furthermore, HBO1 facilitates accumulation of SNF2H and ACF1, an ATP-dependent chromatin remodelling complex, to CPD sites. Depletion of HBO1 inhibited repair of CPDs and sensitized cells to ultraviolet irradiation...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28708932/tandem-repeat-variation-near-the-hic1-hypermethylated-in-cancer-1-promoter-predicts-outcome-of-oxaliplatin-based-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#4
Satoshi Okazaki, Marta Schirripa, Fotios Loupakis, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Martin D Berger, Yuji Miyamoto, Mitsukuni Suenaga, Syma Iqubal, Afsaneh Barzi, Chiara Cremolini, Alfredo Falcone, Francesca Battaglin, Lisa Salvatore, Beatrice Borelli, Timothy G Helentjaris, Heinz-Josef Lenz
BACKGROUND: The hypermethylated in cancer 1/sirtuin 1 (HIC1/SIRT1) axis plays an important role in regulating the nucleotide excision repair pathway, which is the main oxaliplatin-induced damage-repair system. On the basis of prior evidence that the variable number of tandem repeat (VNTR) sequence located near the promoter lesion of HIC1 is associated with HIC1 gene expression, the authors tested the hypothesis that this VNTR is associated with clinical outcome in patients with metastatic colorectal cancer who receive oxaliplatin-based chemotherapy...
July 14, 2017: Cancer
https://www.readbyqxmd.com/read/28707579/the-involvement-of-ercc2-xpd-and-ercc6-csb-wild-type-alleles-in-protection-against-aging-and-cancer
#5
Natalia Savina, Natalia Nikitchenko, Tatyana Kuzhir, Alexander Rolevich, Sergei Krasny, Roza Goncharova
BACKGROUND: DNA helicases maintain genome stability, and their deficiency is associated with disorders resembling premature aging as well as contributes to carcinogenesis. Their functions are determined by the respective genes encoding nucleotide excision repair initiating proteins, e.g. XPD and CSB. OBJECTIVE: The present study aimed to investigate the influence of genetic variations in ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and developing age-related bladder cancer focusing on homozygous wild type alleles...
July 7, 2017: Current Aging Science
https://www.readbyqxmd.com/read/28704716/transcriptional-consequences-of-xpa-disruption-in-human-cell-lines
#6
Mandira Manandhar, Megan G Lowery, Karen S Boulware, Kevin H Lin, Yue Lu, Richard D Wood
Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage...
June 29, 2017: DNA Repair
https://www.readbyqxmd.com/read/28686598/processing-closely-spaced-lesions-during-nucleotide-excision-repair-triggers-mutagenesis-in-e-coli
#7
Régine Janel-Bintz, Rita L Napolitano, Asako Isogawa, Shingo Fujii, Robert P Fuchs
It is generally assumed that most point mutations are fixed when damage containing template DNA undergoes replication, either right at the fork or behind the fork during gap filling. Here we provide genetic evidence for a pathway, dependent on Nucleotide Excision Repair, that induces mutations when processing closely spaced lesions. This pathway, referred to as Nucleotide Excision Repair-induced Mutagenesis (NERiM), exhibits several characteristics distinct from mutations that occur within the course of replication: i) following UV irradiation, NER-induced mutations are fixed much more rapidly (t ½ ≈ 30 min) than replication dependent mutations (t ½ ≈ 80-100 min) ii) NERiM specifically requires DNA Pol IV in addition to Pol V iii) NERiM exhibits a two-hit dose-response curve that suggests processing of closely spaced lesions...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28682600/time-dependent-extension-from-an-8-oxoguanine-lesion-by-human-dna-polymerase-beta
#8
Andrew J Reed, Zucai Suo
The oxidative DNA lesion 7,8-dihydro-2'-deoxyguanine (8-oxoG) often occurs in double-stranded DNA and poses a threat to genomic integrity due to the ability of 8-oxoG to form stable Watson-Crick base pairs with deoxycytidine (8-oxoG:dC) and Hoogsteen base pairs with deoxyadenosine (8-oxoG:dA). In humans, short-patch base excision repair of 8-oxoG:dA base pairs requires human DNA polymerase β (hPolβ) to bypass 8-oxoG. Previously, we have shown hPolβ-catalyzed 8-oxoG bypass to exhibit low fidelity and identified a unique stacking interaction between the newly incorporated nucleotide (dCMP or dAMP) and the templating 8-oxoG...
July 6, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28676700/the-multifaceted-roles-of-parp1-in-dna-repair-and-chromatin-remodelling
#9
REVIEW
Arnab Ray Chaudhuri, André Nussenzweig
Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers...
July 5, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28676261/an-assay-to-detect-dna-damaging-agents-that-induce-nucleotide-excision-repairable-dna-lesions-in-living-human-cells
#10
Reine Takatsuka, Shunsuke Ito, Shigenori Iwai, Isao Kuraoka
Biochemical risk assessment studies of chemicals that induce DNA lesions are important, because lesions in genomic DNA frequently result in cancer, neurodegeneration, and aging in humans. Many classes of DNA lesions induced by chemical agents are eliminated via DNA repair mechanisms, such as nucleotide excision repair (NER) and base excision repair (BER), for the maintenance of genomic integrity. Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28675037/sensitive-detection-of-dna-lesions-by-bulge-enhanced-highly-specific-coamplification-at-lower-denaturation-temperature-polymerase-chain-reaction
#11
Yu Feng, Shuang Cai, Guoliang Xiong, Guanfei Zhang, Shihui Wang, Xin Su, Changyuan Yu
Mutagenic modifications of nucleotides or DNA lesions that result from environmental stress have proven to be associated with a variety of diseases, particularly cancer. The method for accurately detecting the lesions is therefore of great importance for biomedical research and toxicity study. We develop a sensitive and low-cost bulge-enhanced coamplification at lower denaturation temperature polymerase chain reaction (COLD-PCR) method for detecting DNA lesions (uracil and 8-oxoguanine) by combining an in vitro base excision repair (BER) pathway and COLD-PCR...
July 12, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28670762/tribbles-2-mediates-cisplatin-sensitivity-and-dna-damage-response-in-epithelial-ovarian-cancer
#12
Daniel Kritsch, Franziska Hoffmann, Daniel Steinbach, Lars Jansen, Stella Mary Photini, Mieczyslaw Gajda, Alexander S Mosig, Jürgen Sonnemann, Sven Peters, Margarita Melnikova, Jürgen Thomale, Matthias Dürst, Ingo B Runnebaum, Norman Häfner
Aim was to identify methylated genes with functional involvement in cisplatin-resistance development of epithelial ovarian cancer (EOC). Genome-wide analyses of hypermethylated CpG-islands in resistant cell lines in combination with qRT-PCR analyses were used to identify epigenetically silenced genes. EOC-type-II tumors were analyzed for gene methylation and expression and TCGA data were interrogated in-silico. Experiments revealed 37 commonly hypermethylated genes in resistant cells of which Tribbles 2 (TRIB2) showed the most pronounced down-regulation on mRNA level and was characterized further...
July 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28668127/kinetic-methods-for-studying-dna-glycosylases-functioning-in-base-excision-repair
#13
Christopher T Coey, Alexander C Drohat
Base excision repair (BER) is a conserved and ubiquitous pathway that is initiated by DNA glycosylases, which recognize and remove damaged or mismatched nucleobases, setting the stage for restoration of the correct DNA sequence by follow-on BER enzymes. DNA glycosylases employ a nucleotide-flipping step prior to cleavage of the N-glycosyl bond, and most exhibit slow release of the abasic DNA product and/or strong product inhibition. As such, studying the catalytic mechanism of these enzymes requires care in the design, execution, and interpretation of single- and multiple-turnover kinetics experiments, which is the topic of this chapter...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28668122/single-molecule-methods-for-nucleotide-excision-repair-building-a-system-to-watch-repair-in-real-time
#14
Muwen Kong, Emily C Beckwitt, Luke Springall, Neil M Kad, Bennett Van Houten
Single-molecule approaches to solving biophysical problems are powerful tools that allow static and dynamic real-time observations of specific molecular interactions of interest in the absence of ensemble-averaging effects. Here, we provide detailed protocols for building an experimental system that employs atomic force microscopy and a single-molecule DNA tightrope assay based on oblique angle illumination fluorescence microscopy. Together with approaches for engineering site-specific lesions into DNA substrates, these complementary biophysical techniques are well suited for investigating protein-DNA interactions that involve target-specific DNA-binding proteins, such as those engaged in a variety of DNA repair pathways...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28665687/elevated-expression-of-ercc6-confers-resistance-to-5-fluorouracil-and-is-associated-with-poor-patient-survival-in-colorectal-cancer
#15
Zhicheng Zhao, Guojing Zhang, Weidong Li
Excision repair cross-complementation (ERCC) enzymes are key members of the nucleotide excision repair pathway. Dysregulation of ERCC family members has been shown to be involved in chemoresistance in several malignancies. However, the function of ERCC6 in regulating chemo response has not been evaluated in colorectal cancer (CRC). We stably knocked down ERCC6 expression using short hairpin RNA (shRNA) in HCT116 and DLD1 human colon cancer cell lines, followed by chemosensitivity assay. In vivo chemosensitizing effects of ERCC6 were examined in xenograft experiments...
June 30, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28655934/oxidative-stress-induced-by-uva-photoactivation-of-the-tryptophan-uvb-photoproduct-6-formylindolo-3-2-b-carbazole-ficz-inhibits-nucleotide-excision-repair-in-human-cells
#16
Reto Brem, Peter Macpherson, Melisa Guven, Peter Karran
Potentially mutagenic DNA lesions induced by UVB (wavelengths 280-320 nm) are important risk factors for solar ultraviolet (UV) radiation-induced skin cancer. The carcinogenicity of the more abundant UVA (320-400 nm) is less well understood but is generally regarded to reflect its interaction with cellular chromophores that act as photosensitisers. The arylhydrocarbon receptor agonist 6-formylindolo[3,2-b] carbazole (FICZ), is a UVB photoproduct of tryptophan and a powerful UVA chromophore. Combined with UVA, FICZ generates reactive oxygen species (ROS) and induces oxidative DNA damage...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28649747/synthesis-structure-and-biological-evaluation-of-a-platinum-carbazole-conjugate
#17
Young Cheun, Myong-Chul Koag, Youssef W Naguib, Hala Ouzon-Shubeita, Zhengrong Cui, Danaya Pakotiprapha, Seongmin Lee
Cisplatin resistance is caused, in part, by the efficient removal of the helix-distorting cisplatin 1,2-intrastrand crosslinks by nucleotide excision repair (NER) machinery. To make a platinum-DNA adduct that causes less helical distortion than the cisplatin 1,2-intrastrand adduct, we designed and synthesized a monofunctional platinum-carbazole conjugate (carbazoleplatin). The 2.5Å crystal structure of carbazoleplatin-DNA adduct revealed both the monoplatination of the N7 of a guanine (G) base and the intercalation into two G:C base pairs while causing a minor distortion of the DNA helix...
June 26, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28645711/proteome-dynamics-during-post-desiccation-recovery-reveal-convergence-of-desiccation-and-gamma-radiation-stress-response-pathways-in-deinococcus-radiodurans
#18
Aman Kumar Ujaoney, Mahesh Kumar Padwal, Bhakti Basu
Deinococcus radiodurans is inherently resistant to both ionizing radiation and desiccation. Fifteen months of desiccation was found to be the LD50 dose for D. radiodurans. Desiccated cells of D. radiodurans entered 6h of growth arrest during post-desiccation recovery (PDR). Proteome dynamics during PDR were mapped by resolving cellular proteins by 2-dimensional gel electrophoresis coupled with mass spectrometry. At least 41 proteins, represented by 51 spots on proteome profiles, were differentially expressed throughout PDR...
June 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645369/sequencing-dna-for-the-oxidatively-modified-base-8-oxo-7-8-dihydroguanine
#19
Aaron M Fleming, Yun Ding, Cynthia J Burrows
The DNA base guanine (G) can be oxidatively modified to 8-oxo-7,8-dihydroguanine (OG). Extraction of genomic DNA followed by nuclease digestion and mass spectrometry analysis has found OG is present at background levels of ~1 out of 10(6) Gs; however, this approach cannot determine the locations for the OGs in the genome. Thus, in this methods report, we outline three different methods (A, B, and C) for sequencing OG in DNA. Method A sequences OG by utilizing the base excision repair pathway to delete the OG nucleotide from the DNA that is then detected by Sanger sequencing as a deletion signature...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28630130/how-a-genetically-stable-extremophile-evolves-modes-of-genome-diversification-in-the-archaeon-sulfolobus-acidocaldarius
#20
Dominic Mao, Dennis W Grogan
In order to analyze in molecular terms how Sulfolobus genomes diverge, damage-induced mutations and natural polymorphisms (PMs) were identified in laboratory constructs and wild-type isolates, respectively, of Sulfolobus acidocaldarius Among wild-type isolates drawn from one local population, pairwise nucleotide divergence averaged 4 x 10(-6), which is about 0.15% of the corresponding divergence reported for Sulfolobus islandicus The most variable features of wild-type S. acidocaldarius genomes were homopolymer (mononucleotide) tracts and longer tandem repeats, consistent with the spontaneous mutations that occur under laboratory conditions...
June 19, 2017: Journal of Bacteriology
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