Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability
Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability
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DOI：
10.1073/pnas.1232239100
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发表时间：
2003-05-27
影响因子：
11.1
通讯作者：
Kolodner, RD
中科院分区：
文献类型：
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作者：
Myung, K;Pennaneach, V;Kolodner, RD
一些自发的染色体总重排（GCR）似乎是由DNA复制错误引起的。染色质组装因子I（CAF-1）和复制偶联组装因子（RCAF）复合物在DNA复制和修复过程中的染色质组装中发挥作用，并在维持基因组稳定性方面发挥作用。CAF-1或RCAF的失活增加了不同类型GCR的积累速率，包括易位和染色体臂缺失以及相关的从头端粒添加。CAR的失活似乎引起激活DNA损伤检查点的损伤，而RCAF的失活似乎引起激活DNA损伤和复制检查点的损伤。这两种缺陷导致基因组不稳定性增加，通常由这些检查点、RAD 52依赖性重组和PIF 1依赖性抑制从头端粒添加来抑制。与野生型菌株相比，用甲磺酸甲酯处理CAF-1或RCAF缺陷细胞增加了GCR的诱导。这些结果表明，染色质组装与DNA复制和DNA修复的偶联对于维持基因组稳定性至关重要。
Some spontaneous gross chromosomal rearrangements (GCRs) seem to result from DNA-replication errors. The chromatin-assembly factor I (CAF-1) and replication-coupling assembly factor (RCAF) complexes function in chromatin assembly during DNA replication and repair and could play a role in maintaining genome stability. Inactivation of CAF-1 or RCAF increased the rate of accumulating different types of GCRs including translocations and deletion of chromosome arms with associated de novo telomere addition. Inactivation of CAR seems to cause damage that activates the DNA-damage checkpoints, whereas inactivation of RCAF seems to cause damage that activates the DNA-damage and replication checkpoints. Both defects result in increased genome instability that is normally suppressed by these checkpoints, RAD52-dependent recombination, and PIF1-dependent inhibition of de novo telomere addition. Treatment of CAF-1- or RCAF-defective cells with methyl methanesulfonate increased the induction of GCRs compared with that seen for a wild-type strain. These results indicate that coupling of chromatin assembly to DNA replication and DNA repair is critical to maintaining genome stability.