Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells
書誌事項
- 公開日
- 2012-06-28
- 資源種別
- journal article
- 権利情報
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- http://creativecommons.org/licenses/by-nc/3.0
- DOI
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- 10.1093/nar/gks580
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.
収録刊行物
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- Nucleic Acids Research
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Nucleic Acids Research 40 (17), 8406-8415, 2012-06-28
Oxford University Press (OUP)