TY - JOUR
T1 - A checkpoint regulates the rate of progression through S phase in S. cerevisiae in Response to DNA damage
AU - Paulovich, Amanda G.
AU - Hartwell, Leland H.
N1 - Funding Information:
Correspondence should be addressed to L. H. H. We thank T. Weinert and D. Lydall for providing strains and for discussions, S. Bell and B. Stillman for the flow cytometry protocol, members of the labs of L. H. H., B. Byers, W. Fangman/B. Brewer, B. Alberts, and L. Loeb for comments on the manuscript, and especially D. Toczyski for many formative discussions. Supported by grants from the National Institute for General Medical Sciences and the American Cancer Society (to L. H. H.) and a Merck Distinguished Fellow Award (to A. G. P.).
PY - 1995/9/8
Y1 - 1995/9/8
N2 - We demonstrate that in S. cerevisiae the rate of ongoing S phase is slowed when the DNA is subjected to alkylation. Slowing of replication is dependent on the MEC1 and RAD53 genes, indicating that lesions alone do not slow replication in vivo and that the slowing is an active process. While it has been shown that a MEC1- and RAD53-dependent checkpoint responds to blocked replication or DNA damage by inhibiting the onset of mitosis, we demonstrate that this checkpoint must also have an additional target within S phase that controls replication rate. MEC1 is a homolog of the human ATM gene, which is mutated in ataxia telangiectasia (AT) patients. Like mec1 yeast, AT cells are characterized by damage-resistant DNA synthesis, highlighting the congruence of the yeast and mammalian systems.
AB - We demonstrate that in S. cerevisiae the rate of ongoing S phase is slowed when the DNA is subjected to alkylation. Slowing of replication is dependent on the MEC1 and RAD53 genes, indicating that lesions alone do not slow replication in vivo and that the slowing is an active process. While it has been shown that a MEC1- and RAD53-dependent checkpoint responds to blocked replication or DNA damage by inhibiting the onset of mitosis, we demonstrate that this checkpoint must also have an additional target within S phase that controls replication rate. MEC1 is a homolog of the human ATM gene, which is mutated in ataxia telangiectasia (AT) patients. Like mec1 yeast, AT cells are characterized by damage-resistant DNA synthesis, highlighting the congruence of the yeast and mammalian systems.
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U2 - 10.1016/0092-8674(95)90481-6
DO - 10.1016/0092-8674(95)90481-6
M3 - Article
C2 - 7671311
AN - SCOPUS:0029085781
SN - 0092-8674
VL - 82
SP - 841
EP - 847
JO - Cell
JF - Cell
IS - 5
ER -