Abstract：
:Histone H2AX and MDC1 are key DNA repair and DNA-damage signalling proteins. When DNA double-strand breaks (DSBs) occur, H2AX is phosphorylated and then recruits MDC1, which in turn serves as a docking platform to promote the localization of other factors, including 53BP1, to DSB sites. Here, by using CRISPR-Cas9 engineered human cell lines, we identify a hitherto unknown, H2AX-independent, function of MDC1 mediated by its PST-repeat region. We show that the PST-repeat region directly interacts with chromatin via the nucleosome acidic patch and mediates DNA damage-independent association of MDC1 with chromatin. We find that this region is largely functionally dispensable when the canonical γH2AX-MDC1 pathway is operative but becomes critical for 53BP1 recruitment to DNA-damage sites and cell survival following DSB induction when H2AX is not available. Consequently, our results suggest a role for MDC1 in activating the DDR in areas of the genome lacking or depleted of H2AX.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Salguero I,Belotserkovskaya R,Coates J,Sczaniecka-Clift M,Demir M,Jhujh S,Wilson MD,Jackson SPdoi
10.1038/s41467-019-12929-5subject
Has Abstractpub_date
2019-11-15 00:00:00pages
5191issue
1issn
2041-1723pii
10.1038/s41467-019-12929-5journal_volume
10pub_type
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