NAR Breakthrough - PCAF promotes R-loop resolution via histone acetylation
NAR Nucleic Acids Research
Published by Oxford University Press - Impact Factor 16.7
by Seo?Yun Lee, Soo?Hyeon Lee, Nak?Hun Choi, Ja?Young Kim, Jun?Hee Kweon, Kyle?M Miller, and Jae?Jin Kim
R-loops are harmful DNA-RNA hybrid structures that cause genome instability, disrupting normal cell functions. This study explored the role of the protein PCAF in resolving R-loops to maintain genome stability. The researchers found that depleting PCAF leads to increased R-loop formation, especially during transcription, compromising the genome. Mechanistically, PCAF facilitates histone acetylation, recruiting proteins like MRE11, EXO1, FANCM?and BLM to R-loop sites. These proteins collaborate to resolve R-loop structures. The findings suggest that PCAF, histone acetylation, and these repair proteins work together to untangle R-loops and preserve genome integrity. Understanding this process provides insights into R-loop dynamics and PCAF's role in genome maintenance, potentially leading to therapeutic strategies for diseases associated with genome instability, such as cancer.