A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway.
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.
Marchetti
Maria A
MA
Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263-0001, USA.
Kumar
Sanjay
S
Hartsuiker
Edgar
E
Maftahi
Mohamed
M
Carr
Antony M
AM
Freyer
Greg A
GA
Burhans
William C
WC
Huberman
Joel A
JA
D018797:Cell Cycle Proteins / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins; D004720:Endonucleases / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011995:Recombination, Genetic; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; C501395:RAD17 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D004720:Endonucleases; C069266:RAD1 protein, S cerevisiae; C499354:rad1 protein, S pombe; D045643:DNA Repair Enzymes