Proteomic profiling of UV damage repair patches uncovers histone chaperones with central functions in chromatin repair

DNA damage compromises not only genome stability but also the integrity of the chromatin template, which plays a central role in controlling cell identity. Our understanding of chromatin repair mechanisms is very incomplete. To bridge this knowledge gap, here we devise a novel proteomic strategy to characterize dynamic changes in the chromatin landscape during the repair of UV-induced DNA lesions in human cells, in a quantitative, unbiased and time-resolved manner. Thus, we identify the histone chaperones DNAJC9 and MCM2 as central players in chromatin repair. We demonstrate that DNAJC9 and MCM2 are independently recruited to sites of UV damage repair. DNAJC9 provides new H3-H4 histones to CAF-1 and HIRA chaperones for deposition into chromatin and also stimulates old H3-H4 histone recovery. DNAJC9 cooperates with MCM2 to coordinate old and new histone dynamics during UV damage repair. Together, our proteomic dataset provides a molecular framework for further dissecting epigenome maintenance mechanisms.