Faculty, Staff and Student Publications
HP1β Recruits RING1A to Ubiquitinate Histone H2A for BRCA1-Mediated Resection of Double-Stand Breaks
Language
English
Publication Date
2-20-2026
Journal
iScience
DOI
10.1016/j.isci.2025.114582
PMID
41623472
PMCID
PMC12856345
PubMedCentral® Posted Date
12-30-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting H2A lysine 119 ubiquitination. Collective findings reveal a novel mechanism whereby HP1β interactions, mediated through its CSD of HP1β interaction with RING1A, promotes H2AK119 ubiquitination to facilitate BRCA1 recruitment and orchestrate efficient HR and CtIP-dependent DNA resection at DSB sites in gene-rich active chromatin.
Keywords
Biochemistry, Molecular biology
Published Open-Access
yes
Recommended Citation
Charaka, Vijaya; Pandita, Raj K; Tsai, Chi-Lin; et al., "HP1β Recruits RING1A to Ubiquitinate Histone H2A for BRCA1-Mediated Resection of Double-Stand Breaks" (2026). Faculty, Staff and Student Publications. 6577.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6577
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