The yeast Sgs1p helicase acts upstream of Rad53p in the DNA replication checkpoint and colocalizes with Rad53p in S-phase-specific foci

We have examined the cellular function of Sgs1p, a nonessential yeast DNA h elicase, homologs of which are implicated in two highly debilitating heredi tary human diseases (Werner's and Bloom's syndromes). We show that Sgs1p is an integral component of the S-phase checkpoint response in yeast, which a rrests cells due to DNA damage or blocked fork progression during DNA repli cation. DNA pole and Sgs1p are found in the same epistasis group and act up stream of Rad53p to signal cell cycle arrest when DNA replication is pertur bed. Sgs1p is tightly regulated through the cell cycle, accumulates in S ph ase and colocalizes with Rad53p in S-phase-specific foci, even in the absen ce of fork arrest. The association of Rad53p with a chromatin subfraction i s Sgs1p dependent, suggesting an important role for the helicase in the sig nal-transducing pathway that monitors replication fork progression.