Requirement of WDR70 for POLE3-mediated DNA double-strand breaks repair

• DOI: 10.1126/sciadv.adh2358
• Publication Date: 2023-09-08T17:58:54Z
• Authors: Xiaobing Mao; Jian Wu; Qin Zhang; Su Zhang; Xiaoshuang Chen; Xueqin Liu; Mingtian Wei; Xiaowen Wan; Lei Qiu; Ming Zeng; Xue Lei; Cong Liu; Junhong Han
• Keywords: Homology directed repair; Transcription; Ku80

H2BK120ub1 triggers several prominent downstream histone modification pathways and changes in chromatin structure, therefore involving it into multiple critical cellular processes including DNA transcription damage repair. Although has been reported that is mediated by RNF20/40 CRL4 WDR70 , less known about the underlying regulation mechanism for WDR70. By using a series of biochemical cell-based studies, we find promotes interacting with complex, deposition H3K79me2 POLE3 loci highly sensitive to transcription. Moreover, demonstrate interacts CHRAC1 promote repair on expression homology-directed proteins KU80 recruitment identify D121Y mutation colorectal cancer, which leads defect due attenuated interaction POLE3. These findings highlight previously unknown role maintenance genomic stability imply as potential therapeutic targets cancer.