TY - JOUR
T1 - Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irridiation by simulated sunlight
AU - Kozmin, Stanislav G.
AU - Pavlov, Youri I.
AU - Kunkel, Thomas A.
AU - Sage, Evelyne
N1 - Funding Information:
We are grateful to Drs S. Boiteux, L. Gellon and M. de Padula (CEA/CNRS, Fontenay-aux-Roses, France), and D. Nguyen (NIEHS) for help in the can1 gene sequencing. We thank Drs Y. de Rycke and C. Elie (Institut Curie, Section Médicale) for their help in statistical analysis of results. We are thankful to Drs R. M. Schaaper, B. van Houten (NIEHS) and R. Devoret (Institut Curie) for carefully reading the manuscript. This work was supported by Centre National de la Recherche Scientifique (CNRS), Institut Curie and National Institutes of Health. S.K. was a recipient of fellowships from Institut Curie, Association pour la Recherche sur le Cancer and CNRS.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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 η (Polη) and polymerase ζ (Polζ), 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, rad30Δ, rev3Δ and rev3Δ rad30Δ 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 Pohη participates in the non-mutagenic bypass of SSL-dependent cytosine-containing Dewar photoproducts and 8-oxoguanine, while Polζ is mainly responsible for the mutagenic bypass of all types of Dewar photoproducts. They also suggest that in the absence of Polζ, Polη contributes to UVC- and SSL-induced mutagenesis, possibly by the bypass of photodimers containing deaminated cytosine.
AB - 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 η (Polη) and polymerase ζ (Polζ), 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, rad30Δ, rev3Δ and rev3Δ rad30Δ 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 Pohη participates in the non-mutagenic bypass of SSL-dependent cytosine-containing Dewar photoproducts and 8-oxoguanine, while Polζ is mainly responsible for the mutagenic bypass of all types of Dewar photoproducts. They also suggest that in the absence of Polζ, Polη contributes to UVC- and SSL-induced mutagenesis, possibly by the bypass of photodimers containing deaminated cytosine.
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U2 - 10.1093/nar/gkg489
DO - 10.1093/nar/gkg489
M3 - Article
C2 - 12888515
AN - SCOPUS:0042662892
VL - 31
SP - 4541
EP - 4552
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 15
ER -