title: Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.
abstract: 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.
authors: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors: Nami
authors: N
authors: Haruta
authors: Yoshino
authors: Y
authors: Kubota
authors: Takashi
authors: T
authors: Hishida
mesh_terms: D002172:Canavanine / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism / Q000502:physiology*; D003641:Deamination; D017353:Gene Deletion; D016296:Mutagenesis; D011740:Pyrimidine Dimers / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
chemical_list: D002172:Canavanine; D045643:DNA Repair Enzymes; D004259:DNA-Directed DNA Polymerase; D011740:Pyrimidine Dimers; D029701:Saccharomyces cerevisiae Proteins; C072975:RAD14 protein, S cerevisiae; C425929:DNA polymerase zeta; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases