The product of Saccharomyces cerevisiae WHIP/MGS1, a gene related to replication factor C genes, interacts functionally with DNA polymerase delta

Abstract

The Saccharomyces cerevisiae gene WHIP/ MGS1 encodes a protein related to the subunits of Replication Factor C (RFC). We found that the RFC-like motifs in Whip/Mgs1 are essential for its function. Furthermore, by screening for synthetic dosage lethality, we have shown that overexpression of MGS1 causes lethality in combination with mutations in genes that encode replication proteins such as DNA polymerase delta, RFC, PCNA and RPA. Moreover, loss of MGS1 function interferes with the ability of multicopy PCNA to suppress the replication defect of the rfc5-1 mutant. At permissive temperatures, deletion of MGS1 suppresses the hydroxyurea (HU) sensitivity of pol31 and pol32 mutants, which bear mutations in the smaller subunits of DNA polymerase delta, and at semipermissive and non-permissive temperatures mgs1delta partially alleviates the growth defects of the pol31 mutant. We also report that the growth defect and HU sensitivity of the pol31 mutant are suppressed by mms2delta and rad18delta mutations. We suggest that Mgs1 interacts with the DNA replication machinery to modulate the function of DNA polymerase delta during replication or replication-associated repair, and influences the choice of the pathway employed for replication fork reactivation. Possible roles of Mgs1, DNA polymerase delta, Rad18 and Mms2 in replication and replication fork restart are discussed.