Back to Search Start Over

PCAF promotes R-loop resolution via histone acetylation.

Authors :
Lee SY
Lee SH
Choi NH
Kim JY
Kweon JH
Miller KM
Kim JJ
Source :
Nucleic acids research [Nucleic Acids Res] 2024 Aug 27; Vol. 52 (15), pp. 8643-8660.
Publication Year :
2024

Abstract

R-loops cause genome instability, disrupting normal cellular functions. Histone acetylation, particularly by p300/CBP-associated factor (PCAF), is essential for maintaining genome stability and regulating cellular processes. Understanding how R-loop formation and resolution are regulated is important because dysregulation of these processes can lead to multiple diseases, including cancer. This study explores the role of PCAF in maintaining genome stability, specifically for R-loop resolution. We found that PCAF depletion promotes the generation of R-loop structures, especially during ongoing transcription, thereby compromising genome stability. Mechanistically, we found that PCAF facilitates histone H4K8 acetylation, leading to recruitment of the a double-strand break repair protein (MRE11) and exonuclease 1 (EXO1) to R-loop sites. These in turn recruit Fanconi anemia (FA) proteins, including FANCM and BLM, to resolve the R-loop structure. Our findings suggest that PCAF, histone acetylation, and FA proteins collaborate to resolve R-loops and ensure genome stability. This study therefore provides novel mechanistic insights into the dynamics of R-loops as well as the role of PCAF in preserving genome stability. These results may help develop therapeutic strategies to target diseases associated with genome instability.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Details

Language :
English
ISSN :
1362-4962
Volume :
52
Issue :
15
Database :
MEDLINE
Journal :
Nucleic acids research
Publication Type :
Academic Journal
Accession number :
38936834
Full Text :
https://doi.org/10.1093/nar/gkae558