ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin

被引：99

作者：

Lee, Kyoo-young ^{[1
]}

Fu, Haiqing ^{[2
]}

Aladjem, Mirit I. ^{[2
]}

Myung, Kyungjae ^{[1
]}

机构：

[1] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA

[2] NCI, DNA Replicat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF CELL BIOLOGY | 2013年 / 200卷 / 01期

关键词：

CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; FACTOR-C; GENOME STABILITY; S-PHASE; COHESION ESTABLISHMENT; DAMAGE CHECKPOINT; TELOMERE LENGTH; SLIDING CLAMP; FISSION YEAST;

D O I：

10.1083/jcb.201206084

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：31 / 44

页数：14

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