Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irridiation by simulated sunlight

Stanislav G. Kozmin, Youri I. Pavlov, Thomas A. Kunkel, Evelyne Sage

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4541-4552
Number of pages12
JournalNucleic acids research
Volume31
Issue number15
DOIs
StatePublished - Aug 1 2003

Fingerprint

Sunlight
DNA-Directed DNA Polymerase
Saccharomyces cerevisiae
Cytosine
Radiation
Yeasts
DNA
Skin Neoplasms
Mutagenesis
Mutation
Enzymes
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irridiation by simulated sunlight. / Kozmin, Stanislav G.; Pavlov, Youri I.; Kunkel, Thomas A.; Sage, Evelyne.

In: Nucleic acids research, Vol. 31, No. 15, 01.08.2003, p. 4541-4552.

Research output: Contribution to journalArticle

Kozmin, Stanislav G. ; Pavlov, Youri I. ; Kunkel, Thomas A. ; Sage, Evelyne. / Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irridiation by simulated sunlight. In: Nucleic acids research. 2003 ; Vol. 31, No. 15. pp. 4541-4552.
@article{52bf9f64adcf4cecbef04684553002b9,
title = "Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irridiation by simulated sunlight",
abstract = "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.",
author = "Kozmin, {Stanislav G.} and Pavlov, {Youri I.} and Kunkel, {Thomas A.} and Evelyne Sage",
year = "2003",
month = "8",
day = "1",
doi = "10.1093/nar/gkg489",
language = "English (US)",
volume = "31",
pages = "4541--4552",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "15",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=0042662892&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042662892&partnerID=8YFLogxK

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 -