Chk1 prevents abnormal mitosis of S-phase HeLa cells containing DNA damage

	Chk1 prevents abnormal mitosis of S-phase HeLa cells containing DNA damage
	Li, XF; Ward, T; Yao, XB; Wu, JR
刊名	CHINESE SCIENCE BULLETIN
	2009
卷号	54 期号:22 页码:4205-4213
关键词	cell cycle DNA damage checkpoint DNA replication checkpoint Chk1 methyl methanesulfnate
通讯作者	Wu, JR (reprint author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Sch Life Sci, Hefei 230027, Peoples R China.,wujr@sibs.ac.cn
英文摘要	explore effects of DNA damage on cell-cycle progression in p53-deficient tumor cells, synchronized HeLa cells at G1, S and G2/M phases were treated with methyl methanesulfnate (MMS). The results showed that the MMS treatment resulted in the cell-cycle arrest or delay in all 3 phases, while the S-phase cells were the most sensitive to MMS. Further studies demonstrated that ATM-Chk2 and p38 MAPK signaling pathways were activated in all 3 phases when the cells were treated with MMS; whereas Chk1 was activated only in S phase under the drug treatment, indicating that Chk1 specifically participated in S-phase checkpoints. To analyze the role of Chk1 in S-phase checkpoints, we administered a specific Chk1 inhibitor, UCN-01, to the S-phase cells. The results showed that the S-phase cells treated with MMS+UCN-01 could enter aberrant mitosis without finishing DNA replication, indicating that Chk1 mainly functions in the DNA damage checkpoint rather than in the replication checkpoint. In addition, MMS treatment alone inhibited the accumulation of cyclin B1, a key component of M-phase CDK-cyclin complex, in the S-phase cells, whereas the inhibition of Chk1 activation resulted in the accumulation of cyclin B1 in the MMS-treated S-phase cells. This observation further supports the view that DNA-damaged S-phase cells enter abnormal mitosis when Chk1 activation is inhibited. Our results demonstrate that Chk1 is a specific kinase that plays an important role in the MMS-induced S-phase DNA damage checkpoint. As p53 is not involved in this process, Chk1 may be a potential target for p53-deficient tumor therapy.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	REPLICATION FORKS ; CHECKPOINT ; REPAIR ; ACTIVATION ; PHOSPHORYLATION ; MECHANISMS ; EXPRESSION ; PATHWAY ; CLASPIN ; PROTEIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000272034800015
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1285]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, XF,Ward, T,Yao, XB,et al. Chk1 prevents abnormal mitosis of S-phase HeLa cells containing DNA damage[J]. CHINESE SCIENCE BULLETIN,2009,54(22):4205-4213.
APA	Li, XF,Ward, T,Yao, XB,&Wu, JR.(2009).Chk1 prevents abnormal mitosis of S-phase HeLa cells containing DNA damage.CHINESE SCIENCE BULLETIN,54(22),4205-4213.
MLA	Li, XF,et al."Chk1 prevents abnormal mitosis of S-phase HeLa cells containing DNA damage".CHINESE SCIENCE BULLETIN 54.22(2009):4205-4213.