A mitotic topoisomerase II checkpoint in budding yeast is required for genome stability but acts independently of Pds1/securin

被引:33
作者
Andrews, CA
Vas, AC
Meier, B
Giménez-Abián, JF
Díaz-Martínez, LA
Green, J
Erickson, SL
VanderWaal, KE
Hsu, WS
Clarke, DJ [1 ]
机构
[1] Univ Minnesota, Sch Med, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
[2] Ctr Invest Biol, Madrid 28040, Spain
关键词
topoisomerase II; Top2; mitotic checkpoint; catenation; Mad2; Pds1;
D O I
10.1101/gad.1367206
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Topoisomerase II (Topo II) performs topological modifications on double-stranded DNA molecules that are essential for chromosome condensation, resolution, and segregation. In mammals, G2 and metaphase cell cycle delays induced by Topo II poisons have been proposed to be the result of checkpoint activation in response to the catenation state of DNA. However, the apparent lack of such controls in model organisms has excluded genetic proof that Topo II checkpoints exist and are separable from the conventional DNA damage checkpoint controls. But here, we define a Topo II-dependent G2/M checkpoint in a genetically amenable eukaryote, budding yeast, and demonstrate that this checkpoint enhances cell survival. Conversely, a lack of the checkpoint results in aneuploidy. Neither DNA damage-responsive pathways nor Pds1/securin are needed for this checkpoint. Unusually, spindle assembly checkpoint components are required for the Topo II checkpoint, but checkpoint activation is not the result of failed chromosome biorientation or a lack of spindle tension. Thus, compromised Topo II function activates a yeast checkpoint system that operates by a novel mechanism.
引用
收藏
页码:1162 / 1174
页数:13
相关论文
共 61 条
[1]   Genetic evidence for involvement of two distinct nonhomologous end-joining pathways in repair of topoisomerase II-mediated DNA damage [J].
Adachi, N ;
Iiizumi, S ;
So, S ;
Koyama, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 318 (04) :856-861
[2]   CHROMOSOME ASSEMBLY INVITRO - TOPOISOMERASE-II IS REQUIRED FOR CONDENSATION [J].
ADACHI, Y ;
LUKE, M ;
LAEMMLI, UK .
CELL, 1991, 64 (01) :137-148
[3]   The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA Topoisomerase II [J].
Bachant, J ;
Alcasabas, A ;
Blat, Y ;
Kleckner, N ;
Elledge, SJ .
MOLECULAR CELL, 2002, 9 (06) :1169-1182
[4]   Coordination polymers formed by Bi(SC6F5)3 with multidentate polypyridyl ligands [J].
Charmant, JPH ;
Jahan, AHMM ;
Norman, NC ;
Orpen, AG ;
Podesta, TJ .
CRYSTENGCOMM, 2004, 6 :29-33
[5]   INHIBITORY EFFECT OF DIHYDROXYACETONE ON GLUCONOBACTER-OXYDANS - KINETIC ASPECTS AND EXPRESSION BY MATHEMATICAL EQUATIONS [J].
CLARET, C ;
BORIES, A ;
SOUCAILLE, P .
JOURNAL OF INDUSTRIAL MICROBIOLOGY, 1993, 11 (02) :105-112
[6]  
Clarke DJ, 2000, BIOESSAYS, V22, P351, DOI 10.1002/(SICI)1521-1878(200004)22:4<351::AID-BIES5>3.0.CO
[7]  
2-W
[8]   The Pds1 anaphase inhibitor and Mec1 kinase define distinct checkpoints coupling S phase with mitosis in budding yeast [J].
Clarke, DJ ;
Segal, M ;
Mondésert, G ;
Reed, SI .
CURRENT BIOLOGY, 1999, 9 (07) :365-368
[9]   Mec1p regulates Pds1p levels in S phase: complex coordination of DNA replication and mitosis [J].
Clarke, DJ ;
Segal, M ;
Jensen, S ;
Reed, SI .
NATURE CELL BIOLOGY, 2001, 3 (07) :619-627
[10]  
CLARKE DJ, 2003, NAT CELL BIOL, V21, P21