| First Author | Jungmichel S | Year | 2012 |
| Journal | Nucleic Acids Res | Volume | 40 |
| Issue | 9 | Pages | 3913-28 |
| PubMed ID | 22234878 | Mgi Jnum | J:197725 |
| Mgi Id | MGI:5494379 | Doi | 10.1093/nar/gkr1300 |
| Citation | Jungmichel S, et al. (2012) The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator. Nucleic Acids Res 40(9):3913-28 |
| abstractText | Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. Mdc1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail of gammaH2AX following DNA damage, but the role of the N-terminal forkhead-associated (FHA) domain remains unclear. We show that a major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself. Binding to this motif stabilizes a weak self-association of the FHA domain to form a tight dimer. X-ray structures of free and complexed Mdc1 FHA domain reveal a 'head-to-tail' dimerization mechanism that is closely related to that seen in pre-activated forms of the Chk2 DNA damage kinase, and which both positively and negatively influences Mdc1 FHA domain-mediated interactions in human cells prior to and following DNA damage. |
