Identification of MSA1, a cell cycle-regulated, dosage suppressor of drc1/sld2 and dpb11 mutants.

The Dpb11 and Drc1/Sld2 proteins form a complex that is critical for the initiation of DNA replication. In this study we identify MSA1 as a high copy suppressor of a drc1-1 mutant. MSA1 overproduction can also suppress the temperature sensitivity of dpb11-1 and pol2-12 mutants. Reciprocally, msa1 deletion exacerbates the mutant phenotypes of both drc1/sld2 and dpb11 mutants and msa1 deletion alone results in a delay in S phase entry of synchronous cells indicating a positive role for MSA1 in DNA replication. Paradoxically, MSA1 overproduction is deleterious to cdc6-1, cdc7-1, cdc28-1N and cdc14-1 mutants indicating a complex relationship with DNA replication and cell cycle regulatory genes. The Msa1 protein is tightly cell cycle regulated. Msa1 and its paralog, Msa2, both accumulate in highly modified forms just as cells commit to enter S phase and then are rapidly destroyed. MSA1 represents a new cell cycle regulated gene important for S phase entry.