RT Journal Article
SR Electronic
T1 HP1β Chromo Shadow Domain facilitates H2A ubiquitination for BRCA1 recruitment at DNA double-strand breaks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.11.475809
DO 10.1101/2022.01.11.475809
A1 Charaka, Vijaya
A1 Chakraborty, Sharmista
A1 Tsai, Chi-Lin
A1 Wang, Xiaoyan
A1 Pandita, Raj K
A1 Tainer, John A.
A1 Hunt, Clayton R
A1 Pandita, Tej K.
YR 2022
UL http://biorxiv.org/content/early/2022/01/11/2022.01.11.475809.abstract
AB Efficient DNA double strand break (DSB) repair by homologous recombination (HR), as orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we report that Heterochromatin Protein1 beta (HP1β) acts as a key component of the HR DNA resection step by regulating BRCA1 enrichment at DNA damage sites, a function largely dependent on the HP1β chromo shadow domain (CSD). HP1β itself is enriched at DSBs within gene-rich regions through a CSD interaction with Chromatin Assembly Factor 1 (CAF1) and HP1 β depletion impairs subsequent BRCA1 enrichment. An added interaction of the HP1 β CSD with the Polycomb Repressor Complex 1 ubiquitinase component RING1A facilitates BRCA1 recruitment by increasing H2A lysine 118-119 ubiquitination, a marker for BRCA1 recruitment. Our findings reveal that HP1β interactions, mediated through its CSD with RING1A, promote H2A ubiquitination and facilitate BRCA1 recruitment at DNA damage sites, a critical step in DSB repair by the HR pathway. These collective results unveil how HP1β is recruited to DSBs in gene-rich regions and how HP1β subsequently promotes BRCA1 recruitment to further HR DNA damage repair by stimulating CtIP-dependent resection.Competing Interest StatementThe authors have declared no competing interest.