TY - JOUR
T1 - Error-free RAD52 pathway and error-prone REV3 pathway determines spontaneous mutagenesis in Saccharomyces cerevisiae
AU - Endo, Kingo
AU - Tago, Yu Ichiro
AU - Daigaku, Yasukazu
AU - Yamamoto, Kazuo
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007
Y1 - 2007
N2 - Using the CAN1 gene in haploid cells or heterozygous diploid cells, we characterized the effects of mutations in the RAD52 and REV3 genes of Saccharomyces cerevisiae in spontaneous mutagenesis. The mutation rate was 5-fold higher in the haploid rad52 strain and 2.5-fold lower in rev3 than in the wild-type strain. The rate in the rad52 rev3 strain was as low as in the wild-type strain, indicating the rad52 mutator phenotype to be dependent on REV3. Sequencing indicated that G:C→T:A and G:C→C:G transversions increased in the rad52 strain and decreased in the rev3 and rad52 rev3 strains, suggesting a role for REV3 in transversion mutagenesis. In diploid rev3 cells, frequencies of can1Δ::LEU2/can1Δ::LEU2 from CAN1/can1Δ::LEU2 due to recombination were increased over the wild-type level. Overall, in the absence of RAD52, REV3-dependent base-substitutions increased, while in the absence of REV3, RAD52-dependent recombination events increased. We further found that the rad52 mutant had an increased rate of chromosome loss and the rad52 rev3 double mutant had an enhanced chromosome loss mutator phenotype. Taken together, our study indicates that the error-free RAD52 pathway and error-prone REV3 pathway for rescuing replication fork arrest determine spontaneous mutagenesis, recombination, and genome instability.
AB - Using the CAN1 gene in haploid cells or heterozygous diploid cells, we characterized the effects of mutations in the RAD52 and REV3 genes of Saccharomyces cerevisiae in spontaneous mutagenesis. The mutation rate was 5-fold higher in the haploid rad52 strain and 2.5-fold lower in rev3 than in the wild-type strain. The rate in the rad52 rev3 strain was as low as in the wild-type strain, indicating the rad52 mutator phenotype to be dependent on REV3. Sequencing indicated that G:C→T:A and G:C→C:G transversions increased in the rad52 strain and decreased in the rev3 and rad52 rev3 strains, suggesting a role for REV3 in transversion mutagenesis. In diploid rev3 cells, frequencies of can1Δ::LEU2/can1Δ::LEU2 from CAN1/can1Δ::LEU2 due to recombination were increased over the wild-type level. Overall, in the absence of RAD52, REV3-dependent base-substitutions increased, while in the absence of REV3, RAD52-dependent recombination events increased. We further found that the rad52 mutant had an increased rate of chromosome loss and the rad52 rev3 double mutant had an enhanced chromosome loss mutator phenotype. Taken together, our study indicates that the error-free RAD52 pathway and error-prone REV3 pathway for rescuing replication fork arrest determine spontaneous mutagenesis, recombination, and genome instability.
KW - Loss of heterozygosity
KW - RAD52
KW - REV3
KW - Replication fork arrest
KW - Saccharomyces cerevisiae
KW - Spontaneous mutation
UR - http://www.scopus.com/inward/record.url?scp=34047111205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047111205&partnerID=8YFLogxK
U2 - 10.1266/ggs.82.35
DO - 10.1266/ggs.82.35
M3 - Article
C2 - 17396018
AN - SCOPUS:34047111205
VL - 82
SP - 35
EP - 42
JO - Genes and Genetic Systems
JF - Genes and Genetic Systems
SN - 1341-7568
IS - 1
ER -