TY - JOUR
T1 - The effect of oxidative metabolism on spontaneous Polζ-dependent translesion synthesis in Saccharomyces cerevisiae
AU - Minesinger, Brenda K.
AU - Abdulovic, Amy L.
AU - Ou, Tingwei M.
AU - Jinks-Robertson, Sue
N1 - Funding Information:
We would like to thank Dr. David M. Guidot for advice on the construction of the anaerobic system and the members of the SJR laboratory for critically reading this manuscript. This work was supported by grant GM64769 to SJR from the National Institutes of Heath. BKM and ALA were partially supported by the Graduate Division of Biological and Biomedical Sciences of Emory University.
PY - 2006/2/3
Y1 - 2006/2/3
N2 - DNA lesions can stall or block high-fidelity polymerases, thus inhibiting replication. To bypass such lesions, low-fidelity translesion synthesis (TLS) polymerases can be used to insert a nucleotide across from the lesion or extend from a lesion:base mispair. When DNA repair is compromised in Saccharomyces cerevisiae, spontaneous DNA lesions can lead to a novel mutational event in which a frameshift is accompanied by one or more base pair substitutions. These "complex frameshifts" are dependent upon the TLS polymerase Polζ, and provide a mutational signature for mutagenic Polζ-dependent activity. In the current study, we have found that a specific subset of the Polζ-dependent mutational events requires oxidative metabolism. These results suggest that translesion bypass of spontaneously oxidized DNA bases can be a significant source of mutagenesis in repair compromised cells.
AB - DNA lesions can stall or block high-fidelity polymerases, thus inhibiting replication. To bypass such lesions, low-fidelity translesion synthesis (TLS) polymerases can be used to insert a nucleotide across from the lesion or extend from a lesion:base mispair. When DNA repair is compromised in Saccharomyces cerevisiae, spontaneous DNA lesions can lead to a novel mutational event in which a frameshift is accompanied by one or more base pair substitutions. These "complex frameshifts" are dependent upon the TLS polymerase Polζ, and provide a mutational signature for mutagenic Polζ-dependent activity. In the current study, we have found that a specific subset of the Polζ-dependent mutational events requires oxidative metabolism. These results suggest that translesion bypass of spontaneously oxidized DNA bases can be a significant source of mutagenesis in repair compromised cells.
KW - Oxidative damage
KW - Polymerase zeta
KW - Reactive oxygen species
KW - Spontaneous DNA damage
KW - Translesion synthesis
UR - http://www.scopus.com/inward/record.url?scp=30444449018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30444449018&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2005.10.002
DO - 10.1016/j.dnarep.2005.10.002
M3 - Article
C2 - 16290107
AN - SCOPUS:30444449018
SN - 1568-7864
VL - 5
SP - 226
EP - 234
JO - DNA Repair
JF - DNA Repair
IS - 2
ER -