title: The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage.
abstract: In wild-type Saccharomyces cerevisiae, a checkpoint slows the rate of progression of an ongoing S phase in response to exposure to a DNA-alkylating agent. Mutations that eliminate S phase regulation also confer sensitivity to alkylating agents, leading us to suggest that, by regulating the S phase rate, cells are either better able to repair or better able to replicate damaged DNA. In this study, we determine the effects of mutations that impair S phase regulation on the ability of excision repair-defective cells to replicate irreparably UV-damaged DNA. We assay survival after UV irradiation, as well as the genetic consequences of replicating a damaged template, namely mutation and sister chromatid exchange induction. We find that RAD9, RAD17, RAD24, and MEC3 are required for UV-induced (although not spontaneous) mutagenesis, and that RAD9 and RAD17 (but not REV3, RAD24, and MEC3) are required for maximal induction of replication-dependent sister chromatid exchange. Therefore, checkpoint genes not only control cell cycle progression in response to damage, but also play a role in accommodating DNA damage during replication.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Paulovich
authors.forename: C D
authors.initials: CD
authors.lastname: Armour
authors.forename: L H
authors.initials: LH
authors.lastname: Hartwell
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D001483:Base Sequence; D004249:DNA Damage; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009692:Nucleic Acid Heteroduplexes; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D012854:Sister Chromatid Exchange; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers; D009692:Nucleic Acid Heteroduplexes