Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts.
Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts.
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DOI：
10.1083/jcb.200508100
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发表时间：
2005-12-19
期刊：
影响因子：
--
通讯作者：
Michael WM
中科院分区：
文献类型：
--
作者：
Leach CA;Michael WM
同源三聚体DNA复制蛋白增殖细胞核抗原受泛素化和总甲基化的调节。我们研究了这些修饰的外观和对青蛙卵提取液中染色体复制的影响。非洲爪哇的增殖细胞核抗原是通过苏莫化、单泛素化和二泛素化修饰在赖氨酸164上的。苏莫化和单泛素化发生在未损伤DNA的复制过程中，而二泛素化则发生在对DNA损伤的反应中。当赖氨酸164的修饰被阻止时，复制叉通过未受损的dna的移动减慢，dna聚合酶δ不能与复制的染色质相联系。当单独阻止总甲基化时，复制正常发生，简单单链DNA模板的复制既不需要单糖基化也不需要总甲基化。我们的发现通过阐明这些修饰在未受损DNA复制过程中的作用，扩展了增殖细胞核抗原泛素化和总甲基化的功能谱系。此外，他们认为，在S期，增殖细胞核抗原的单苷酸化可能是控制复制体运动速度的分子气门。
The homotrimeric DNA replication protein proliferating cell nuclear antigen (PCNA) is regulated by both ubiquitylation and sumoylation. We study the appearance and the impact of these modifications on chromosomal replication in frog egg extracts. Xenopus laevis PCNA is modified on lysine 164 by sumoylation, monoubiquitylation, and diubiquitylation. Sumoylation and monoubiquitylation occur during the replication of undamaged DNA, whereas diubiquitylation occurs specifically in response to DNA damage. When lysine 164 modification is prevented, replication fork movement through undamaged DNA slows down and DNA polymerase δ fails to associate with replicating chromatin. When sumoylation alone is prevented, replication occurs normally and neither monoubiquitylation nor sumoylation are required for the replication of simple single-strand DNA templates. Our findings expand the repertoire of functions for PCNA ubiquitylation and sumoylation by elucidating a role for these modifications during the replication of undamaged DNA. Furthermore, they suggest that PCNA monoubiquitylation serves as a molecular gas pedal that controls the speed of replisome movement during S phase.
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