RAD9-DEPENDENT-G(1) ARREST DEFINES A 2ND CHECKPOINT FOR DAMAGED DNA IN THE CELL-CYCLE OF SACCHAROMYCES-CEREVISIAE

Exposure of the yeast Saccharomyces cerevisiae to ultraviolet (UV) lig ht, the UV-mimetic chemical 4-nitroquinoline-1-oxide (4NQO), or gamma radiation after release from G1 arrest induced by alpha factor results in delayed resumption of the cell cycle. As is the case with G2 arres t following ionizing radiation damage [Weinert, T. A. & Hartwell, L. H . (1988) Science 241, 317-322], the normal execution of DNA damage-ind uced G1 arrest depends on a functional yeast RAD9 gene. We suggest tha t the RAD9 gene product may interact with cellular components common t o the G1/S and G2/M transition points in the cell cycle of this yeast. These observations define a checkpoint in the eukaryotic cell cycle t hat may facilitate the repair of lesions that are otherwise processed to lethal and/or mutagenic damage during DNA replication. This checkpo int apparently operates after the mating pheromone-induced G1 arrest p oint but prior to replicative DNA synthesis, S phase-associated maxima l induction of histone H2A mRNA, and bud emergence.