| First Author | Hung PJ | Year | 2018 |
| Journal | Mol Cell | Volume | 71 |
| Issue | 2 | Pages | 332-342.e8 |
| PubMed ID | 30017584 | Mgi Jnum | J:265834 |
| Mgi Id | MGI:6202149 | Doi | 10.1016/j.molcel.2018.06.018 |
| Citation | Hung PJ, et al. (2018) MRI Is a DNA Damage Response Adaptor during Classical Non-homologous End Joining. Mol Cell 71(2):332-342.e8 |
| abstractText | The modulator of retrovirus infection (MRI or CYREN) is a 30-kDa protein with a conserved N-terminal Ku-binding motif (KBM) and a C-terminal XLF-like motif (XLM). We show that MRI is intrinsically disordered and interacts with many DNA damage response (DDR) proteins, including the kinases ataxia telangiectasia mutated (ATM) and DNA-PKcs and the classical non-homologous end joining (cNHEJ) factors Ku70, Ku80, XRCC4, XLF, PAXX, and XRCC4. MRI forms large multimeric complexes that depend on its N and C termini and localizes to DNA double-strand breaks (DSBs), where it promotes the retention of DDR factors. Mice deficient in MRI and XLF exhibit embryonic lethality at a stage similar to those deficient in the core cNHEJ factors XRCC4 or DNA ligase IV. Moreover, MRI is required for cNHEJ-mediated DSB repair in XLF-deficient lymphocytes. We propose that MRI is an adaptor that, through multivalent interactions, increases the avidity of DDR factors to DSB-associated chromatin to promote cNHEJ. |
