Defective S phase chromatin assembly causes DNA damage, activation of the S phase checkpoint, and S phase arrest

被引:212
作者
Ye, XF
Franco, AA
Santos, H
Nelson, DM
Kaufman, PD
Adams, PD [1 ]
机构
[1] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA
[2] Lawrence Berkeley Natl Lab, Donner Lab 351, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
关键词
D O I
10.1016/S1097-2765(03)00037-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The S phase checkpoint protects the genome from spontaneous damage during DNA replication, although the cause of damage has been unknown. We used a dominant-negative mutant of a subunit of CAF-I, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S phase chromatin assembly and found that this induced S phase arrest. Arrest was accompanied by DNA damage and S phase checkpoint activation and required ATR or ATM kinase activity. These results show that in human cells CAF-I activity is required for completion of S phase and that a defect in chromatin assembly can itself induce DNA damage. We propose that errors in chromatin assembly, occurring spontaneously or caused by genetic mutations or environmental agents, contribute to genome instability.
引用
收藏
页码:341 / 351
页数:11
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