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MRI is a DNA damage response adaptor during classical non-homologous end joining

Mol Cell. 2018-07; 
Hung PJ, Johnson B, Chen BR, Byrum AK, Bredemeyer AL, Yewdell WT, Johnson TE, Lee BJ, Deivasigamani S, Hindi I, Amatya P, Gross ML, Paull TT, Pisapia DJ, Chaudhuri J, Petrini JJH, Mosammaparast N, Amarasinghe GK, Zha S, Tyler JK, Sleckman BP
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Bacterial Expression System The coding regions of the mouse MRI and human MRI genes were codon-optimized for expression in E. coli (GenScript) and used as templates to subclone the coding regions into a modified pET15b vector (Novagen). Get A Quote

摘要

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 c... More

关键词

CYREN; DNA double-strand break repair; MRI; V(D)J recombination; adaptor protein; non-homologous end joining