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Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

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.

Pubmed ID: 22743272

Authors

  • Haruta N
  • Kubota Y
  • Hishida T

Journal

Nucleic acids research

Publication Data

September 1, 2012

Associated Grants

None

Mesh Terms

  • Canavanine
  • DNA Damage
  • DNA Repair
  • DNA Repair Enzymes
  • DNA-Directed DNA Polymerase
  • Deamination
  • Gene Deletion
  • Mutagenesis
  • Pyrimidine Dimers
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ultraviolet Rays