Nature Cell Biology5, 928 - 935 (2003)
Published online: 21 September 2003; | doi:10.1038/ncb1046
S-phase checkpoint controls mitosis via an APC-independent Cdc20p function
Duncan J. Clarke1, 2, Marisa Segal1, 3, Catherine A. Andrews2, Stanislav G. Rudyak1, Sanne Jensen1, 4, Karen Smith2
& Steven I. Reed1
1
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
2
Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, 420 Washington Avenue SE, Minneapolis, Minnesota 55455, USA.
3
Present address: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
4
Present address: Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark.
Correspondence should be addressed to Steven I. Reed sreed@scripps.edu
Cells divide with remarkable fidelity, allowing complex organisms to develop and possess longevity. Checkpoint controls contribute by ensuring that genome duplication and segregation occur without error so that genomic instability, associated with developmental abnormalities and a hallmark of most human cancers1,
2,
3,
4,
5, is avoided. S-phase checkpoints prevent cell division while DNA is replicating6,
7,
8. Budding yeast Mec1p and Rad53p, homologues of human checkpoint kinases ATM/ATR and Chk2, are needed for this control system. How Mec1p and Rad53p prevent mitosis in S phase is not known. Here we provide evidence that budding yeasts avoid mitosis during S phase by regulating the anaphase-promoting complex (APC) specificity factor Cdc20p: Mec1p and Rad53p repress the accumulation of Cdc20p in S phase. Because precocious Cdc20p accumulation causes anaphase onset and aneuploidy, Cdc20p concentrations must be precisely regulated during each and every cell cycle. Catastrophic mitosis induced by Cdc20p in S phase occurs even in the absence of core APC components. Thus, Cdc20p can function independently of the APC.
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