CDK phosphorylation of Drc1 regulates DNA replication in fission yeast

被引:51
作者
Noguchi, E
Shanahan, P
Noguchi, C
Russell, P [1 ]
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0960-9822(02)00739-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclin-dependent kinases (CDKs) are absolutely required for DNA replication in eukaryotic cells [1, 2]. CDKs are thought to activate one or more replication factors, but the identities of these proteins are unknown. Here we describe fission yeast Drc1, a protein required for DNA replication that is phosphorylated by Cdc2. Drc1 depletion leads to catastrophic mitotic divisions with incompletely replicated DNA, indicating that Drc1 is required for DNA synthesis and S-M replication checkpoint control. Drc1 associates with Cdc2 and is phosphorylated at the onset of S phase when Cdc2 is activated. Mutant Drc1 that lacks CDK phosphorylation sites is nonfunctional and fails to interact with Cut5 replication factor. These data suggest that Cdc2 promotes DNA replication by phosphorylating Drc1 and regulating its association with Cut5.
引用
收藏
页码:599 / 605
页数:7
相关论文
共 27 条
[1]   DPB11, WHICH INTERACTS WITH DNA-POLYMERASE II(EPSILON) IN SACCHAROMYCES-CEREVISIAE, HAS A DUAL ROLE IN S-PHASE PROGRESSION AND AT A CELL-CYCLE CHECKPOINT [J].
ARAKI, H ;
LEEM, SH ;
PHONGDARA, A ;
SUGINO, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (25) :11791-11795
[2]   Regulation of the G1 phase of the cell cycle by periodic stabilization and degradation of the p25rum1 CDK inhibitor [J].
Benito, J ;
Martín-Castellanos, C ;
Moreno, S .
EMBO JOURNAL, 1998, 17 (02) :482-497
[3]   The stability of the Cdc6 protein is regulated by cyclin-dependent kinase/cyclin B complexes in Saccharomyces cerevisiae [J].
Calzada, A ;
Sánchez, M ;
Sánchez, E ;
Bueno, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (13) :9734-9741
[4]   The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle [J].
Drury, LS ;
Perkins, G ;
Diffley, JFX .
CURRENT BIOLOGY, 2000, 10 (05) :231-240
[5]   Phosphorylation controls timing of Cdc6p destruction: A biochemical analysis [J].
Elsasser, S ;
Chi, Y ;
Yang, P ;
Campbell, JL .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (10) :3263-3277
[6]   A single fission yeast mitotic cyclin B p34(cdc2) kinase promotes both S-phase and mitosis in the absence of G(1) cyclins [J].
Fisher, DL ;
Nurse, P .
EMBO JOURNAL, 1996, 15 (04) :850-860
[7]  
Greenwood E, 1998, J CELL SCI, V111, P3101
[8]   A predictive scale for evaluating cyclin-dependent kinase substrates - A comparison of p34(cdc2) and p33(cdk2) [J].
Holmes, JK ;
Solomon, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (41) :25240-25246
[9]   Rum1 and Cdc18 link inhibition of cyclin-dependent kinase to the initiation of DNA replication in Schizosaccharomyces pombe [J].
Jallepalli, PV ;
Kelly, TJ .
GENES & DEVELOPMENT, 1996, 10 (05) :541-552
[10]   Regulation of the replication initiator protein p65(cdc18) by CDK phosphorylation [J].
Jallepalli, PV ;
Brown, GW ;
MuziFalconi, M ;
Tien, D ;
Kelly, TJ .
GENES & DEVELOPMENT, 1997, 11 (21) :2767-2779