title: ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin.
abstract: 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.
authors.affiliation: Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kyoo-young
authors.initials: KY
authors.lastname: Lee
authors.forename: Haiqing
authors.initials: H
authors.lastname: Fu
authors.forename: Mirit I
authors.initials: MI
authors.lastname: Aladjem
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Myung
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016196:S Phase / Q000502:physiology*
chemical_list: C546328:ATAD5 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities