Stabilization of microtubule dynamics at anaphase onset promotes chromosome segregation

被引:151
作者
Higuchi, T [1 ]
Uhlmann, F [1 ]
机构
[1] Canc Res UK London Res Inst, Chromosome Segregat Lab, Lincolns Inn Fields Labs, London WC2A 3PX, England
关键词
D O I
10.1038/nature03240
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Microtubules of the mitotic spindle form the structural basis for chromosome segregation. In metaphase, microtubules show high dynamic instability, which is thought to aid the 'search and capture' of chromosomes for bipolar alignment on the spindle. Microtubules suddenly become more stable at the onset of anaphase, but how this change in microtubule behaviour is regulated and how important it is for the ensuing chromosome segregation are unknown(1-4). Here we show that in the budding yeast Saccharomyces cerevisiae, activation of the phosphatase Cdc14 at anaphase onset is both necessary and sufficient for silencing microtubule dynamics. Cdc14 is activated by separase, the protease that triggers sister chromatid separation, linking the onset of anaphase to microtubule stabilization(5,6). If sister chromatids separate in the absence of Cdc14 activity, microtubules maintain high dynamic instability; this correlates with defects in both the movement of chromosomes to the spindle poles (anaphase A) and the elongation of the anaphase spindle (anaphase B). Cdc14 promotes localization of microtubule-stabilizing proteins to the anaphase spindle, and dephosphorylation of the kinetochore component Ask1 contributes to both the silencing of microtubule turnover and successful anaphase A.
引用
收藏
页码:171 / 176
页数:6
相关论文
共 30 条
[11]   Real time observation of anaphase in vitro [J].
Murray, AW ;
Desai, AB ;
Salmon, ED .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (22) :12327-12332
[12]   Cyclin B destruction triggers changes in kinetochore behavior essential for successful anaphase [J].
Parry, DH ;
Hickson, GRX ;
O'Farrell, PH .
CURRENT BIOLOGY, 2003, 13 (08) :647-653
[13]   Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14 [J].
Pereira, G ;
Schiebel, E .
SCIENCE, 2003, 302 (5653) :2120-2124
[14]   Separase, polo kinase, the kinetochore protein Slk19 and Spo12 function in a network that controls Cdc14 localization during early anaphase [J].
Stegmeier, F ;
Visintin, R ;
Amon, A .
CELL, 2002, 108 (02) :207-220
[15]   Mitosis in living budding yeast: Anaphase a but no metaphase plate [J].
Straight, AF ;
Marshall, WF ;
Sedat, JW ;
Murray, AW .
SCIENCE, 1997, 277 (5325) :574-578
[16]   Time-lapse microscopy reveals unique roles for kinesins during anaphase in budding yeast [J].
Straight, AF ;
Sedat, JW ;
Murray, AW .
JOURNAL OF CELL BIOLOGY, 1998, 143 (03) :687-694
[17]   Cdc14 phosphatase induces rDNA condensation and resolves cohesin-independent cohesion during budding yeast anaphase [J].
Sullivan, M ;
Higuchi, T ;
Katis, VL ;
Uhlmann, F .
CELL, 2004, 117 (04) :471-482
[18]   Studies on substrate recognition by the budding yeast separase [J].
Sullivan, M ;
Hornig, NCD ;
Porstmann, T ;
Uhlmann, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (02) :1191-1196
[19]   A non-proteolytic function of separase links the onset of anaphase to mitotic exit [J].
Sullivan, M ;
Uhlmann, F .
NATURE CELL BIOLOGY, 2003, 5 (03) :249-254
[20]   DESTRUCTION OF THE CDC28 CLB MITOTIC KINASE IS NOT REQUIRED FOR THE METAPHASE TO ANAPHASE TRANSITION IN BUDDING YEAST [J].
SURANA, U ;
AMON, A ;
DOWZER, C ;
MCGREW, J ;
BYERS, B ;
NASMYTH, K .
EMBO JOURNAL, 1993, 12 (05) :1969-1978