| Literature DB >> 31875566 |
Mi-Sun Kang1, Jinwoo Kim2, Eunjin Ryu2, Na Young Ha1, Sunyoung Hwang1, Byung-Gyu Kim1, Jae Sun Ra1, Yeong Jae Kim2, Jung Me Hwang1, Kyungjae Myung3, Sukhyun Kang4.
Abstract
Proliferating cell nuclear antigen (PCNA) is a DNA clamp essential for DNA replication. During DNA synthesis, PCNA is continuously loaded onto and unloaded from DNA. PCNA recruits various proteins to nascent DNA to facilitate chromosome duplication. Therefore, timely PCNA unloading is crucial for high-fidelity DNA replication. The ATAD5-RFC-like complex (ATAD5-RLC) unloads PCNA from replicated DNA. It is unclear how ATAD5-RLC activity is regulated to prevent premature PCNA unloading. Here, we find that BRD4, an acetyl-histone-binding chromatin reader, inhibits the PCNA-unloading activity of ATAD5-RLC. The BRD4 ET domain interacts with a region upstream of the ATAD5 PCNA-unloading domain. BRD4-ATAD5 binds to acetyl-histones in nascent chromatin. BRD4 release from chromatin correlates with PCNA unloading. Disruption of the interaction between BRD4 and acetyl-histones or between BRD4 and ATAD5 reduces the PCNA amount on chromatin. In contrast, the overexpression of BRD4 increases the amount of chromatin-bound PCNA. Thus, acetyl-histone-bound BRD4 fine-tunes PCNA unloading from nascent DNA.Entities:
Keywords: ATAD5; BET protein; BRD4; DNA replication; PCNA; PCNA unloading; RFC-like complex; histone acetylation; nascent chromatin
Mesh：
Substances：
Year: 2019 PMID： 31875566 DOI： 10.1016/j.celrep.2019.11.114
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423