Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination.
To investigate the DNA damage response, we undertook a genome-wide study in Saccharomyces cerevisiae and identified 86 gene deletions that lead to increased levels of spontaneous Rad52 foci in proliferating diploid cells. More than half of the genes are conserved across species ranging from yeast to humans. Along with genes involved in DNA replication, repair, and chromatin remodeling, we found 22 previously uncharacterized open reading frames. Analysis of recombination rates and synthetic genetic interactions with rad52Delta suggests that multiple mechanisms are responsible for elevated levels of spontaneous Rad52 foci, including increased production of recombinogenic lesions, sister chromatid recombination defects, and improper focus assembly/disassembly. Our cell biological approach demonstrates the diversity of processes that converge on homologous recombination, protect against spontaneous DNA damage, and facilitate efficient repair.
Alvaro
David
D
Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.
Lisby
Michael
M
Rothstein
Rodney
R
D001483:Base Sequence; D017124:Conserved Sequence; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D017353:Gene Deletion; D016681:Genome, Fungal; D015698:Genomic Library; D019656:Loss of Heterozygosity; D008938:Mitosis / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D004271:DNA, Fungal; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins