A TOPOISOMERASE II-DEPENDENT G2 CYCLE CHECKPOINT IN MAMMALIAN-CELLS

被引:283
作者
DOWNES, CS [1 ]
CLARKE, DJ [1 ]
MULLINGER, M [1 ]
GIMENEZABIAN, JF [1 ]
CREIGHTON, AM [1 ]
JOHNSON, RT [1 ]
机构
[1] UNIV LONDON ST BARTHOLOMEWS HOSP & MED COLL,DEPT REPROD PHYSIOL,MED CHEM LAB,LONDON EC1A 7BE,ENGLAND
关键词
D O I
10.1038/372467a0
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
THE enzyme DNA topoisomerase II, which removes the catenations formed between the DNA molecules of sister chromatids during replication(1) and is a structural component of chromosome cores(2), is needed for chromosome condensation in yeast(3) and in Xenopus extracts(4-6). Inhibitors of topoisomerase II arrest mammalian cells before mitosis in the G2 phase of the cell cycle(7), but also produce DNA damage, which causes arrest through established checkpoint controls(8). It is open to question whether cells need topoisomerase II to leave G2, or control late-cycle progression in response to its activity. Bisdioxopiperazines are topoisomerase II inhibitors that act without producing direct DNA damage(9); the most potent, ICRF-193, blocks mammalian entry into but not exit from mitosis. Here we show that checkpoint-evading agents such as caffeine override this block to produce abortively condensed chromosomes, indicating that topoisomerase II is needed for complete condensation. We find that exit from G2 is regulated by a catenation-sensitive checkpoint mechanism which is distinct from the G2-damage checkpoint.
引用
收藏
页码:467 / 470
页数:4
相关论文
共 30 条
[1]   CHROMOSOME ASSEMBLY INVITRO - TOPOISOMERASE-II IS REQUIRED FOR CONDENSATION [J].
ADACHI, Y ;
LUKE, M ;
LAEMMLI, UK .
CELL, 1991, 64 (01) :137-148
[2]   RADIATION-INDUCED SINGLE-STRAND BREAKS IN DNA DETERMINED BY RATE OF ALKALINE STRAND SEPARATION AND HYDROXYLAPATITE CHROMATOGRAPHY - ALTERNATIVE TO VELOCITY SEDIMENTATION [J].
AHNSTROM, G ;
EDVARDSSON, KA .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1974, 26 (05) :493-497
[3]  
CLARKE DJ, 1993, J CELL SCI, V105, P563
[4]   THE NUCLEOSKELETON AND THE TOPOLOGY OF REPLICATION [J].
COOK, PR .
CELL, 1991, 66 (04) :627-635
[5]   ANTITUMOUR ACTIVITY IN A SERIES OF BISDIKETOPIPERAZINES [J].
CREIGHTON, AM ;
HELLMANN, K ;
WHITECROSS, S .
NATURE, 1969, 222 (5191) :384-+
[6]  
CREIGHTON AM, 1979, ADV MED ONCOL RES ED, V5, P83
[7]  
Downes CS, 1991, P NATL ACAD SCI USA, V88, P2616
[8]  
GORBSKY GJ, 1994, CANCER RES, V54, P1042
[9]   TOPOISOMERASE-II DOES NOT PLAY A SCAFFOLDING ROLE IN THE ORGANIZATION OF MITOTIC CHROMOSOMES ASSEMBLED IN XENOPUS EGG EXTRACTS [J].
HIRANO, T ;
MITCHISON, TJ .
JOURNAL OF CELL BIOLOGY, 1993, 120 (03) :601-612
[10]  
ISHIDA R, 1991, CANCER RES, V51, P4909