A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway
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In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 11, 28.05.2002, p. 7472-7.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway
AU - Marchetti, Maria A
AU - Kumar, Sanjay
AU - Hartsuiker, Edgar
AU - Maftahi, Mohamed
AU - Carr, Antony M
AU - Freyer, Greg A
AU - Burhans, William C
AU - Huberman, Joel A
PY - 2002/5/28
Y1 - 2002/5/28
N2 - 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.
AB - 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.
KW - Cell Cycle Proteins
KW - DNA Damage
KW - DNA Repair
KW - DNA Repair Enzymes
KW - DNA Replication
KW - DNA-Binding Proteins
KW - Endonucleases
KW - Humans
KW - Nuclear Proteins
KW - Proliferating Cell Nuclear Antigen
KW - Recombination, Genetic
KW - S Phase
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
KW - Schizosaccharomyces
KW - Schizosaccharomyces pombe Proteins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, P.H.S.
U2 - 10.1073/pnas.112702399
DO - 10.1073/pnas.112702399
M3 - Article
C2 - 12032307
VL - 99
SP - 7472
EP - 7477
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 11
ER -