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A genetic screen to discover pathways affecting cohesin function in Schizosaccharomyces pombe identifies chromatin effectors.

ABSTRACT: Cohesion, the force that holds sister chromatids together from the time of DNA replication until separation at the metaphase to anaphase transition, is mediated by the cohesin complex. This complex is also involved in DNA damage repair, chromosomes condensation, and gene regulation. To learn more about the cellular functions of cohesin, we conducted a genetic screen in Schizosaccharomyces pombe with two different cohesin mutants (eso1-G799D and mis4-242). We found synthetic negative interactions with deletions of genes involved in DNA replication and heterochromatin formation. We also found a few gene deletions that rescued the growth of eso1-G799D at the nonpermissive temperature, and these genes partially rescue the lagging chromosome phenotype. These genes are all chromatin effectors. Overall, our screen revealed an intimate association between cohesin and chromatin.

SUBMITTER: Chen Z

PROVIDER: S-EPMC3464108 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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A genetic screen to discover pathways affecting cohesin function in Schizosaccharomyces pombe identifies chromatin effectors.

Chen Zhiming Z McCrosky Scott S Guo Weichao W Li Hua H Gerton Jennifer L JL

G3 (Bethesda, Md.) 20121001 10

Cohesion, the force that holds sister chromatids together from the time of DNA replication until separation at the metaphase to anaphase transition, is mediated by the cohesin complex. This complex is also involved in DNA damage repair, chromosomes condensation, and gene regulation. To learn more about the cellular functions of cohesin, we conducted a genetic screen in Schizosaccharomyces pombe with two different cohesin mutants (eso1-G799D and mis4-242). We found synthetic negative interactions ...[more]

PMID: 23050226

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Project description:In fission yeast the intra-S phase and DNA damage checkpoints are activated in response to inhibition of DNA replication or DNA damage, respectively. The intra-S phase checkpoint responds to stalled replication forks leading to the activation of the Cds1 kinase that both delays cell cycle progression and stabilizes DNA replication forks. The DNA damage checkpoint, that operates during the G2 phase of the cell cycle delays mitotic progression through activation of the checkpoint kinase, Chk1. Delay of the cell cycle is believed to be essential to allow time for either replication restart (in S phase) or DNA damage repair (in G2). Previously, our laboratory showed that fission yeast cells deleted for the N-terminal half of DNA polymerase ? (Cdc20) are delayed in S phase, but surprisingly require Chk1 rather than Cds1 to maintain cell viability. Several additional DNA replication mutants were then tested for their dependency on Chk1 or Cds1 when grown under semi-permissive temperatures. We discovered that mutants defective in DNA replication initiation are sensitive only to loss of Chk1, whilst mutations that inhibit DNA replication elongation are sensitive to loss of both Cds1 and Chk1. To confirm that the Chk1-sensitive, Cds1-insensitive phenotype (rid phenotype) is specific to mutants defective in DNA replication initiation, we completed a genetic screen for cell cycle mutants that require Chk1, but not Cds1 to maintain cell viability when grown at semi-permissive temperatures. Our screen identified two mutants, rid1-1 and rid2-1, that are defective in Orc1 and Mcm4, respectively. Both mutants show defects in DNA replication initiation consistent with our hypothesis that the rid phenotype is replication initiation specific. In the case of Mcm4, the mutation has been mapped to a highly conserved region of the protein that appears to be required for DNA replication initiation, but not elongation. Therefore, we conclude that the cellular response to inhibition of DNA replication initiation is distinct from blocking DNA replication elongation, and this difference can be exploited to identify mutants specifically defective in DNA replication initiation.

Dataset Information

A genetic screen to discover pathways affecting cohesin function in Schizosaccharomyces pombe identifies chromatin effectors.

Publications

A genetic screen to discover pathways affecting cohesin function in Schizosaccharomyces pombe identifies chromatin effectors.

Similar Datasets

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