| First Author | Bhargava R | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 2484 |
| PubMed ID | 29950655 | Mgi Jnum | J:267957 |
| Mgi Id | MGI:6209359 | Doi | 10.1038/s41467-018-04867-5 |
| Citation | Bhargava R, et al. (2018) C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains. Nat Commun 9(1):2484 |
| abstractText | To investigate the fidelity of canonical non-homologous end joining (C-NHEJ), we developed an assay to detect EJ between distal ends of two Cas9-induced chromosomal breaks that are joined without causing insertion/deletion mutations (indels). Here we find that such EJ requires several core C-NHEJ factors, including XLF. Using variants of this assay, we find that C-NHEJ is required for EJ events that use 1-2, but not >/=3, nucleotides of terminal microhomology. We also investigated XLF residues required for EJ without indels, finding that one of two binding domains is essential (L115 or C-terminal lysines that bind XRCC4 and KU/DNA, respectively), and that disruption of one of these domains sensitizes XLF to mutations that affect its dimer interface, which we examined with molecular dynamic simulations. Thus, C-NHEJ, including synergistic function of distinct XLF domains, is required for EJ of chromosomal breaks without indels. |
