Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts.

Huang, Juch Chin; Hsu, David S.; Kazantsev, Aleksey G.; Sancar, Aziz

doi:10.1073/pnas.91.25.12213

Cited by 223 publications

(183 citation statements)

References 30 publications

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“…Further, NER does not seem to play any role in MMS resistance in mammalian fibroblasts (43). While the list of known in vitro substrates for NER has expanded from just DNA helix-distorting lesions to include O 6 -methylguanine, AP sites, N 6 -methyladenine, and some mismatched bases, it is not yet known whether 3MeA is repaired by NER (17,22). Given the biological evidence presented here and similar studies in S. cerevisiae, it seems highly likely that 3MeA can be repaired by NER, at least in S. pombe and S. cerevisiae (48).…”

Section: Discussionmentioning

confidence: 99%

“…However, in vivo studies revealed a role for NER in the repair of methylated DNA base lesions that do not cause major helical distortions and in providing cellular resistance to simple methylating agents (38,48,49). Indeed, biochemical studies confirmed that subtle types of DNA damage can be substrates for NER, including thymine glycols, 8-oxoguanine, O 4 -ethylthymine, O 4 -methylthymine, O 6 -methylguanine, AP sites, and N 6 -methyladenine (17,22,26,36,38,46). Thus, NER may play a role in alkylation resistance larger than was originally thought.…”

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confidence: 99%

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Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

Memişoğlu

Samson

2000

J Bacteriol

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DNA damage is unavoidable, and organisms across the evolutionary spectrum possess DNA repair pathways that are critical for cell viability and genomic stability. To understand the role of base excision repair (BER) in protecting eukaryotic cells against alkylating agents, we generated Schizosaccharomyces pombe strains mutant for the mag1 3-methyladenine DNA glycosylase gene. We report that S. pombe mag1 mutants have only a slightly increased sensitivity to methylation damage, suggesting that Mag1-initiated BER plays a surprisingly minor role in alkylation resistance in this organism. We go on to show that other DNA repair pathways play a larger role than BER in alkylation resistance. Mutations in genes involved in nucleotide excision repair (rad13) and recombinational repair (rhp51) are much more alkylation sensitive than mag1 mutants. In addition, S. pombe mutant for the flap endonuclease rad2 gene, whose precise function in DNA repair is unclear, were also more alkylation sensitive than mag1 mutants. Further, mag1 and rad13 interact synergistically for alkylation resistance, and mag1 and rhp51 display a surprisingly complex genetic interaction. A model for the role of BER in the generation of alkylation-induced DNA strand breaks in S. pombe is discussed.DNA damage emanates from the inherent chemical instability of nucleic acids, from errors made by DNA polymerase during DNA replication, and from exposure to DNA-damaging agents present in the environment or produced by certain endogenous cellular processes (reviewed in reference 15). All organisms possess a panel of DNA repair mechanisms to repair damaged DNA. DNA excision repair pathways recognize and remove damaged segments from one DNA strand and then resynthesize new DNA, using the opposing undamaged strand as a template. Excision repair includes base excision repair (BER) and nucleotide excision repair (NER). An alternative approach to handling damaged DNA is by recombinational repair. These DNA repair pathways have been best characterized in Escherichia coli, but analogous pathways have been found in all organisms examined to date (15).BER initiation occurs by the action of DNA glycosylases that recognize specific types of damaged or abnormal DNA bases and cleave the glycosylic bond linking the base to the sugarphosphate backbone. DNA glycosylases recognize bases such as uracil, deaminated adenine (hypoxanthine), and certain alkylated and oxidized purines and pyrimidines (reviewed in references 10, 15, 21, 31, and 47). Releasing a damaged base from the DNA produces an apurinic/apyrimidinic (AP) site, and it is worth noting that AP sites are themselves a form of DNA damage. In addition to being generated by DNA glycosylases, AP sites can be formed spontaneously. AP endonucleases (which cleave 5Ј to the AP site) or AP lyases (which cleave 3Ј to the AP site) cleave the DNA backbone adjacent to the AP site. AP endonuclease produces a 5Ј-deoxyribose phosphate moiety, which must be removed to allow subsequent DNA ligation; removal occurs by the action of deoxyr...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

Memişoğlu

Samson

2000

J Bacteriol

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“…It is commonly known that DNA oxidative damage is repaired via activation of both BER and NER pathways, based on the severity of DNA damage [13][14][15][16]29] . Theoretically, DNA repair function should be activated once DNA damage occurs in the cells.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that OGG1 activity is inversely related to the level of 8-oxodG in brain regions [12] . Alternatively, oxidative DNA damage can be repaired by nucleotide excision repair (NER) [13][14][15][16][17][18] , which is a major DNA repair pathway in removing a wide range of DNA damage including DNA double helix distortion [19] . Approximately 20-30 proteins are involved in NER, participating in successive steps of damage recognition, local opening of the DNA double helix around the injury, incision of the damaged strand on either side of the lesion, and nascent DNA synthesis/ligation [19] .…”

Section: Introductionmentioning

confidence: 99%

1-Methyl-4-phenyl-pyridinium time-dependently alters expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group F protein in PC12 cells

Yang

Sun

2010

Neurosci. Bull.

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Objective To determine if DNA excision repair enzymes oxoguanine glycosylase 1 (OGG1) and xeroderma pigmentosum group F protein (XPF) are involved in the pathogenesis of Parkinson's disease (PD) in a cell model. Methods PC12 cells were treated with 1-Methyl-4-phenylpyridine ion (MPP + ) for various periods of time to induce oxidative DNA damage. MTT assay was used to determine cell viability. Immunocytochemistry with antibody against 8-hydroxy-2'-deoxyguanosine (8-oxodG) was used to evaluate oxidative DNA damage. Immunoblotting was used to detect the protein levels of OGG1 and XPF. Results MPP + treatment (1 mmol/L) for 18 h and 24 h reduced cell viability to 78.6% and 70.3% of the control, respectively, in a time-dependent way. MPP + increased the immunoreactivity of 8-oxodG in the cytoplasm at 3 h and in the nucleus at 24 h of treatment. With the treatment of MPP + , the expression of OGG1 was significantly increased at 1 h, reaching a peak at 3 h, and then it was decreased at 24 h, as compared to that with vehicle treatment. The same effect was exerted on XPF level, except that the XPF level reached a peak at 18 h of MPP + treatment. Moreover, the maximally-increased protein level of OGG1 by MPP + was approximately 2-fold higher than that of XPF. Conclusion MPP + treatment could timedependently induce increases in OGG1 and XPF expressions in PC12 cells. Also, this study indicates that the base and nucleotide excision repair pathways may be compensatorily activated in the early stage of pathogenesis in the cells after MPP + treatment.

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“…An exceptional example has been the cloning and characterization of several nucleotide excision repair (NER) genes from cell lines derived from patients with xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy (1,2). This complex repair system can recognize a broad spectrum of DNA lesions such as UV photoproducts, bulky chemical adducts, alkylating chemical adducts, crosslinks and, to a lesser extent, abasic sites and mismatches (3,4). Another recent development has been the identification ofhuman homologues of bacterial MutS (hMSH2) and MutL (hMLH1, hPMS1, hPMS2) (5).…”

Section: Introductionmentioning

confidence: 99%

Mammalian assay for site-specific DNA damage processing using the human H-rasproto-oncogene

Arcangeli

Williams

1995

Nucl Acids Res

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The human genomic H-ras proto-oncogene was inserted into an Epstein-Barr virus (EBV) vector (p220.2) that replicates synchronously with the cell cycle. Unique restriction enzyme sites, 30 bp apart, were created on either side of codon 12 to enable the construction of gapped heteroduplex (GHD) DNA. Depending upon experimental protocol, the gap could be located either on the coding (non-transcribed) strand or the non-coding (transcribed) strand. GHD DNA was created using a 1.8 kb segment of H-ras DNA containing exon 1, into which a synthetic 30 nucleotide oligomer containing a strand-and site-specific mismatched nucleotide was annealed. The 1.8 kb segment of H-ras DNA containing a codon 12; middle G:T, A:C or T:C mismatch has been religated with high efficiency into the EBV vector and transfected into NIH 3T3 cells using a mild liposome-mediated protocol. Subsequent hygromycin resistant NIH 3T3 colonies have been PCR amplified and sequenced. In this study, codon 12; middle nucleotide mismatch correction rates to wild-type G:C during replication in NIH 3T3 cells were 96.4% of G:T mismatches, 87.5% of A:C mismatches and 67% of T:C mismatches.

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Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts.

Cited by 223 publications

References 30 publications

Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

1-Methyl-4-phenyl-pyridinium time-dependently alters expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group F protein in PC12 cells

Mammalian assay for site-specific DNA damage processing using the human H-rasproto-oncogene

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