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PCNA Unloading Is Negatively Regulated by BET Proteins
Mi-Sun Kang1, Jinwoo Kim2, Eunjin Ryu2
1Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Cell Reports
|December 26, 2019
Summary
BRD4, a chromatin reader, inhibits the unloading of Proliferating Cell Nuclear Antigen (PCNA) from DNA. This regulation by BRD4 ensures high-fidelity DNA replication by fine-tuning PCNA unloading during synthesis.
Area of Science:
- Molecular Biology
- Epigenetics
- Chromatin Biology
Background:
- Proliferating Cell Nuclear Antigen (PCNA) is vital for DNA replication, acting as a sliding clamp.
- Efficient DNA replication requires timely loading and unloading of PCNA from DNA.
- The ATAD5-RFC-like complex (ATAD5-RLC) is responsible for unloading PCNA from replicated DNA.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling ATAD5-RLC activity.
- To identify factors that prevent premature PCNA unloading during DNA replication.
Main Methods:
- Investigated the interaction between BRD4 and the ATAD5-RLC complex.
- Utilized chromatin immunoprecipitation assays to assess protein binding.
- Examined the effect of BRD4 modulation on PCNA levels at chromatin.
Main Results:
- BRD4 inhibits the PCNA-unloading activity of ATAD5-RLC.
- BRD4's ET domain interacts with a region upstream of the ATAD5 PCNA-unloading domain.
- BRD4 binds to acetyl-histones in nascent chromatin, and its release correlates with PCNA unloading.
- Disrupting BRD4 interactions or overexpressing BRD4 alters chromatin-bound PCNA levels.
Conclusions:
- BRD4 acts as a negative regulator of PCNA unloading by ATAD5-RLC.
- BRD4 fine-tunes PCNA unloading from nascent DNA through interaction with acetyl-histones.
- This mechanism ensures high-fidelity DNA replication by controlling PCNA dynamics.
Keywords:
ATAD5BET proteinBRD4DNA replicationPCNAPCNA unloadingRFC-like complexhistone acetylationnascent chromatinMore Related Videos
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