Defective S phase chromatin assembly causes DNA damage, activation of the S phase checkpoint, and S phase arrest
Defective S phase chromatin assembly causes DNA damage, activation of the S phase checkpoint, and S phase arrest
复制标题
DOI：
10.1016/s1097-2765(03)00037-6
复制
发表时间：
2003-02-01
期刊：
影响因子：
16
通讯作者：
Adams, PD
中科院分区：
文献类型：
--
作者：
Ye, XF;Franco, AA;Adams, PD
S期检查点保护基因组免受DNA复制过程中的自发损伤，尽管损伤的原因尚不清楚。我们使用caf - 1亚基的显性阴性突变体来抑制S期染色质组装，并发现这诱导了S期阻滞。caf - 1是一种将新合成的DNA组装成核小体的复合物。阻滞伴随着DNA损伤和S期检查点激活，需要ATR或ATM激酶活性。这些结果表明，在人类细胞中，cafi活性是完成S期所必需的，染色质组装缺陷本身可以诱导DNA损伤。我们提出染色质组装中的错误，自发发生或由基因突变或环境因素引起，有助于基因组不稳定。
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.