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DOI

  • Maria A Marchetti
    Roswell Park Cancer Institute, Buffalo, NY
  • Sanjay Kumar
    Roswell Park Cancer Institute, Buffalo, NY
  • Edgar Hartsuiker
    University of Sussex
  • Mohamed Maftahi
    Columbia University, New York
  • Antony M Carr
    University of Sussex
  • Greg A Freyer
    Columbia University, New York
  • William C Burhans
    Roswell Park Cancer Institute, Buffalo, NY
  • Joel A Huberman
    Roswell Park Cancer Institute, Buffalo, NY

The eukaryotic intra-S-phase checkpoint, which slows DNA synthesis in response to DNA damage, is poorly understood. Is DNA damage recognized directly, or indirectly through its effects on replication forks? Is the slowing of S phase in part because of competition between DNA synthesis and recombination/repair processes? The results of our genetic analyses of the intra-S-phase checkpoint in the fission yeast, Schizosaccharomyces pombe, suggest that the slowing of S phase depends weakly on the helicases Rqh1 and Srs2 but not on other recombination/repair pathways. The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1, and on Rad4/Cut5 (similar to budding yeast Dpb11, which interacts with DNA polymerase epsilon) but not on Rhp9 (similar to budding yeast Rad9, necessary for direct damage recognition). These results suggest that, in fission yeast, the signal activating the intra-S-phase checkpoint is generated only when replication forks encounter DNA damage.

Keywords

  • Cell Cycle Proteins, DNA Damage, DNA Repair, DNA Repair Enzymes, DNA Replication, DNA-Binding Proteins, Endonucleases, Humans, Nuclear Proteins, Proliferating Cell Nuclear Antigen, Recombination, Genetic, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
Original languageEnglish
Pages (from-to)7472-7
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number11
DOIs
Publication statusPublished - 28 May 2002
Externally publishedYes
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