Roles of Saccharomyces cerevisiae DNA polymerases Poleta and Polzeta in response to irradiation by simulated sunlight.
Sunlight causes lesions in DNA that if unrepaired and inaccurately replicated by DNA polymerases yield mutations that result in skin cancer in humans. Two enzymes involved in translesion synthesis (TLS) of UV-induced photolesions are DNA polymerase eta (Poleta) and polymerase zeta (Polzeta), encoded by the RAD30A and REV3 genes, respectively. Previous studies have investigated the TLS roles of these polymerases in human and yeast cells irradiated with monochromatic, short wavelength UVC radiation (254 nm). However, less is known about cellular responses to solar radiation, which is of higher and mixed wavelengths (310-1100 nm) and produces a different spectrum of DNA lesions, including Dewar photoproducts and oxidative lesions. Here we report on the comparative cytotoxic and mutagenic effects of simulated sunlight (SSL) and UVC radiation on yeast wild-type, rad30Delta, rev3Delta and rev3Delta rad30Delta strains. The results with SSL support several previous interpretations on the roles of these two polymerases in TLS of photodimers and (6-4) photoproducts derived from studies with UVC. They further suggest that Poleta participates in the non-mutagenic bypass of SSL-dependent cytosine-containing Dewar photoproducts and 8-oxoguanine, while Polzeta is mainly responsible for the mutagenic bypass of all types of Dewar photoproducts. They also suggest that in the absence of Polzeta, Poleta contributes to UVC- and SSL-induced mutagenesis, possibly by the bypass of photodimers containing deaminated cytosine.
Kozmin
Stanislav G
SG
CNRS-IC UMR 2027, Institut Curie, Bât. 110, Centre Universitaire, F-91405 Orsay, France.
Pavlov
Youri I
YI
Kunkel
Thomas A
TA
Sage
Evelyne
E
D001483:Base Sequence; D002470:Cell Survival / Q000528:radiation effects; D003596:Cytosine / Q000032:analysis; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D005800:Genes, Fungal / Q000528:radiation effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D008027:Light; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D000099270:Y-Family DNA Polymerases
D003596:Cytosine; D004271:DNA, Fungal; D004259:DNA-Directed DNA Polymerase; D006147:Guanine; D011740:Pyrimidine Dimers; D029701:Saccharomyces cerevisiae Proteins; C024829:8-hydroxyguanine; C092602:REV3 protein, S cerevisiae; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases