Topoisomerase II and histone deacetylase inhibitors delay the G2/M transition by triggering the p38 MAPK checkpoint pathway.
Topoisomerase II and histone deacetylase inhibitors delay the G2/M transition by triggering the p38 MAPK checkpoint pathway.
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DOI：
10.1083/jcb.200405167
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发表时间：
2004-08-16
期刊：
影响因子：
--
通讯作者：
Rieder CL
中科院分区：
文献类型：
--
作者：
Mikhailov A;Shinohara M;Rieder CL
当早期前期PtK1或印度猕猴细胞暴露于拓扑异构酶II （topo II）抑制剂，诱导很少的DNA损伤时，它们被延迟进入有丝分裂。我们发现这种延迟通过抑制p38而不是ATM激酶而被覆盖。用高渗介质或组蛋白去乙酰化酶抑制剂处理早期前期细胞同样会延迟进入有丝分裂，这种延迟也可以通过抑制p38来防止。总之，这些结果揭示了在G2延迟进入有丝分裂期间，通过激活p38 MAPK检查点，独立于atm介导的DNA损伤检查点，诱导染色质拓扑结构全局变化的药物或胁迫。该途径的存在消除了假设G2期间存在多个“染色质修饰”检查点的必要性。最后，在topo II抑制剂存在的情况下进入有丝分裂的细胞形成中期纺锤体，通过纺锤体组装而不是p38检查点延迟进入后期。
When early prophase PtK1 or Indian muntjac cells are exposed to topoisomerase II (topo II) inhibitors that induce little if any DNA damage, they are delayed from entering mitosis. We show that this delay is overridden by inhibiting the p38, but not the ATM, kinase. Treating early prophase cells with hyperosmotic medium or a histone deacetylase inhibitor similarly delays entry into mitosis, and this delay can also be prevented by inhibiting p38. Together, these results reveal that agents or stresses that induce global changes in chromatin topology during G2 delay entry into mitosis, independent of the ATM-mediated DNA damage checkpoint, by activating the p38 MAPK checkpoint. The presence of this pathway obviates the necessity of postulating the existence of multiple “chromatin modification” checkpoints during G2. Lastly, cells that enter mitosis in the presence of topo II inhibitors form metaphase spindles that are delayed in entering anaphase via the spindle assembly, and not the p38, checkpoint.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
64.8
作者：
DOWNES, CS;CLARKE, DJ;JOHNSON, RT
通讯作者：
JOHNSON, RT
影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
10.5
作者：
Brancho, D;Tanaka, N;Davis, RJ
通讯作者：
Davis, RJ
影响因子：
21.3
作者：
Fernandez-Capetillo, O;Chen, HT;Nussenzweig, A
通讯作者：
Nussenzweig, A