Article
- The EMBO Journal (2002) 21, 3370 - 3376
- doi:10.1093/emboj/cdf346
Subject Category:
G1/S CDK is inhibited to restrain mitotic onset when DNA replication is blocked in fission yeast
Patrick Zarzov1,2, Anabelle Decottignies1, Giuseppe Baldacci2 and Paul Nurse1
- Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
- Institut Curie Recherche, Bat. 110, Centre Universitaire, F-91405 Orsay, France
Correspondence to:
Patrick Zarzov, E-mail: zarzov@curie.u-psud.fr
Received 29 August 2001; Accepted 9 May 2002; Revised 7 May 2002
Abstract
Cyclin-dependent kinase (CDK) Tyr15 phosphorylation plays a major role in regulating G2/M CDKs, but the role of this phosphorylation in regulating G1/S CDKs is less clear. We have studied the regulation and function of Cdc2-Tyr15 phosphorylation in the fission yeast Schizosaccharomyces pombe G1/S CDK Cig2/Cdc2. This complex is subject to high level Cdc2-Tyr15 phosphorylation inhibiting its kinase activity in hydroxyurea-treated cells blocked in S-phase. We show that this Tyr15 phosphorylation is required to maintain efficient mitotic checkpoint arrest, because Cig2 accumulates during the block and this accumulation can advance mitotic onset. This mitotic induction operates, at least in part, through activation of the normal G2/M CDK complex Cdc13/Cdc2. Thus, Tyr15 phosphorylation of G1/S CDK complexes is important in the checkpoint control blocking mitotic onset when DNA replication is inhibited.
Keywords:
- Cdc2,
- Cig2,
- checkpoint,
- mitosis,
- Tyr15
