ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin.
ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin.
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DOI：
10.1083/jcb.201206084
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发表时间：
2013-01-07
期刊：
影响因子：
--
通讯作者：
Myung K
中科院分区：
文献类型：
--
作者：
Lee KY;Fu H;Aladjem MI;Myung K
ATAD5 的减少通过保留染色质上的 PCNA 和其他复制体蛋白来延长复制工厂的寿命，从而导致不活跃的复制工厂增加并降低总体复制率。复制工厂的时间和空间调控对于有效的 DNA 复制非常重要。然而，潜在的分子机制尚不清楚。在这里，我们报告 ATAD5 调节复制工厂的寿命。 ATAD5 表达的减少通过在 DNA 合成期间甚至之后在染色质上保留增殖细胞核抗原 (PCNA) 和其他复制体蛋白来延长复制工厂的寿命。这导致不活跃的复制工厂增加，复制体蛋白积累。因此，总体复制率降低，导致 S 期进展延迟。 ATAD5 耗尽后 G2 期细胞中 PCNA 灶的普遍检测表明，复制工厂分解的缺陷在 S 期完成后仍然存在。 ATAD5 介导的复制工厂和 PCNA 调节需要完整的 ATAD5 ATP 酶结构域。总而言之，我们的数据表明 ATAD5 可能通过其 PCNA 卸载活动来调节 DNA 复制工厂的周期。
Reduction of ATAD5 extends the lifespan of replication factories by retaining PCNA and other replisome proteins on chromatin, leading to an increase in inactive replication factories and reduced overall replication rate. Temporal and spatial regulation of the replication factory is important for efficient DNA replication. However, the underlying molecular mechanisms are not well understood. Here, we report that ATAD5 regulates the lifespan of replication factories. Reduced expression of ATAD5 extended the lifespan of replication factories by retaining proliferating cell nuclear antigen (PCNA) and other replisome proteins on the chromatin during and even after DNA synthesis. This led to an increase of inactive replication factories with an accumulation of replisome proteins. Consequently, the overall replication rate was decreased, which resulted in the delay of S-phase progression. Prevalent detection of PCNA foci in G2 phase cells after ATAD5 depletion suggests that defects in the disassembly of replication factories persist after S phase is complete. ATAD5-mediated regulation of the replication factory and PCNA required an intact ATAD5 ATPase domain. Taken together, our data imply that ATAD5 regulates the cycle of DNA replication factories, probably through its PCNA-unloading activity.
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DOI：
10.1073/pnas.95.20.11607
发表时间：
1998-09-29
影响因子：
11.1
作者：
Cai, JS;Yao, NN;Hurwitz, J
通讯作者：
Hurwitz, J
DOI：
10.1073/pnas.93.23.12896
发表时间：
1996-11-12
影响因子：
11.1
作者：
Cai, JS;Uhlmann, F;Hurwitz, J
通讯作者：
Hurwitz, J
影响因子：
14.9
作者：
Kim J;Robertson K;Mylonas KJ;Gray FC;Charapitsa I;MacNeill SA
通讯作者：
MacNeill SA
DOI：
10.1083/jcb.149.2.271
发表时间：
2000-04-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Leonhardt H;Rahn HP;Weinzierl P;Sporbert A;Cremer T;Zink D;Cardoso MC
通讯作者：
Cardoso MC
影响因子：
3.5
作者：
Fox JT;Lee KY;Myung K
通讯作者：
Myung K