A ROLE FOR DNA PRIMASE IN COUPLING DNA-REPLICATION TO DNA-DAMAGE RESPONSE

The temperature-sensitive yeast DNA primase mutant pri1-M4 fails to ex ecute an early step of DNA replication and exhibits a dominant, allele -specific sensitivity to DNA-damaging agents. pri1-M4 is defective in slowing down the rate of S phase progression and partially delaying th e G(1)-S transition in response to DNA damage. Conversely, the G(2) DN A damage response and the S-M checkpoint coupling completion of DNA re plication to mitosis are unaffected. The signal transduction pathway l eading to Rad53p phosphorylation induced by DNA damage is proficient i n pri1-M4, and cell cycle delay caused by Rad53p overexpression is cou nteracted by the pri1-M4 mutation. Altogether, our results suggest tha t DNA primase plays an essential role in a subset of the Rad53p-depend ent checkpoint pathways controlling cell cycle progression in response to DNA damage.