Alternative replication factor C protein, Elg1, maintains chromosome stability by regulating PCNA levels on chromatin.

Abstract

Proliferating cell nuclear antigen (PCNA) is loaded on chromatin upon initiation of the S phase and acts as a platform for a large number of proteins involved in chromosome duplication at the replication fork. As duplication is completed, PCNA dissociates from chromatin, and thus, chromatin-bound PCNA levels are regulated during the cell cycle. Although the mechanism of PCNA loading has been extensively investigated, the unloading mechanism has remained unclear. Here, we show that Elg1, an alternative replication factor C protein, is required for the regulation of chromatin-bound PCNA levels. When Elg1 was depleted by small interfering RNA, chromatin-bound PCNA levels were extremely increased during the S phase. The number of PCNA foci, regions in the nucleus normally representing DNA replication sites, was increased and PCNA remained on chromatin after DNA replication. Various chromatin-associated protein levels on chromatin were affected, and chromatin loop size was increased. During mitosis, cells with aberrant chromosomes and lagging chromosomes were frequently detected. Our findings suggest that Elg1 has an important role in maintaining chromosome integrity by regulating PCNA levels on chromatin, thereby acting as a PCNA unloading factor.

• Authors: Yasushi Shiomi, Hideo Nishitani
• Journal: Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 18 Issue 11 Pg. 946-59 (Nov 2013) ISSN: 1365-2443 [Electronic] England
• PMID: 23937667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Chemical References

• ATAD5 protein, human
• Chromatin
• DNA-Binding Proteins
• Proliferating Cell Nuclear Antigen
• Adenosine Triphosphatases
• ATPases Associated with Diverse Cellular Activities
• Replication Protein C

Topics

• ATPases Associated with Diverse Cellular Activities
• Adenosine Triphosphatases (genetics, metabolism)
• Cell Cycle
• Cell Line, Tumor
• Chromatin (metabolism)
• Chromosomal Instability
• DNA-Binding Proteins (genetics, metabolism)
• G2 Phase
• Humans
• Proliferating Cell Nuclear Antigen (metabolism)
• Replication Protein C (metabolism)
• S Phase