Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage–modified chromatin

• DOI: 10.1083/jcb.200708210
• Publication Date: 2008-04-17T22:27:39Z
• Authors: Fredrik Melander; Simon Bekker-Jensen; Jacob Falck; Jiri Bartek; Niels Mailand; Jiri Lukas
• Keywords: Nijmegen breakage syndrome; Rad50

DNA double-strand breaks (DSBs) trigger accumulation of the MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on DSB-flanking chromatin facilitates survival. Chromatin MRN requires MDC1 adaptor protein, but mechanism behind MRN-MDC1 interaction is unknown. We show that NBS1 subunit interacts with N terminus enriched in Ser-Asp-Thr (SDT) repeats. This was constitutive and mediated by binding between phosphorylated SDT repeats phosphate-binding forkhead-associated domain NBS1. Phosphorylation casein kinase 2 (CK2) sufficient to MDC1-NBS1 vitro, associated CK2 activity cells. Inhibition reduced phosphorylation vivo, disruption SDT-associated phosphoacceptor sites prevented at DSBs. Together, these data suggest functions recruit and, thereby, increases local concentration chromosomal breakage.