Mutations in SID2, a novel gene in saccharomyces cerevisiae, cause synthetic lethality with sic1 deletion and may cause a defect during S phase

Matthew D. Jacobson, Claudia X. Muñoz, Kirstin S. Knox, Beth E. Williams, Lenette L. Lu, Frederick R. Cross, Elizabeth A. Vallen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

SIC1 encodes a nonessential B-type cyclin/CDK inhibitor that functions at the G1/S transition and the exit from mitosis. To understand more completely the regulation of these transitions, mutations causing synthetic lethality with sic1Δ were isolated. In this screen, we identified a novel gene, SID2, which encodes an essential protein that appears to be required for DNA replication or repair, sid2-1 sic1Δ strains and sid2-21 temperature-sensitive strains arrest preanaphase as large-budded cells with a single nucleus, a short spindle, and an ∼2C DNA content. RAD9, which is necessary for the DNA damage checkpoint, is required for the preanaphase arrest of sid2-1 sic1Δ cells. Analysis of chromosomes in mutant sid2-21 cells by field inversion gel electrophoresis suggests the presence of replication forks and bubbles at the arrest. Deleting the two S phase cyclins, CLB5 and CLB6, substantially suppresses the sid2-1 sic1Δ inviability, while stabilizing Clb5 protein exacerbates the defects of sid2-1 sic1Δ cells. In synchronized sid2-1 mutant strains, the onset of replication appears normal, but completion of DNA synthesis is delayed, sid2-1 mutants are sensitive to hydroxyurea indicating that sid2-1 cells may suffer DNA damage that, when combined with additional insult, leads to a decrease in viability. Consistent with this hypothesis, sid2-1 rad9 cells are dead or very slow growing even when SIC1 is expressed.

Original languageEnglish (US)
Pages (from-to)17-33
Number of pages17
JournalGenetics
Volume159
Issue number1
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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