Nej1 interacts with Mre11 to regulate tethering and Dna2 binding at DNA double-strand breaks Journal Article
| Authors: | Mojumdar, A.; Sorenson, K.; Hohl, M.; Toulouze, M.; Lees-Miller, S. P.; Dubrana, K.; Petrini, J. H. J.; Cobb, J. A. |
| Article Title: | Nej1 interacts with Mre11 to regulate tethering and Dna2 binding at DNA double-strand breaks |
| Abstract: | Non-homologous end joining (NHEJ) and homologous recombination (HR) are the two major pathways of DNA double-strand break (DSB) repair and both are highly conserved from yeast to mammals. Nej1 has a role in DNA end-tethering at a DSB, and the Mre11/Rad50/Xrs2 (MRX) complex is important for its recruitment to the break. Nej1 and Dna2-Sgs1 interact with the C-terminal end of Mre11, which also includes the region where Rad50 binds. By characterizing the functionality of Nej1 in two rad50 mutants, which alter the structural features of MRX, we demonstrate that Nej1 inhibits the binding of Dna2 to Mre11 and Sgs1. Nej1 interactions with Mre11 promote tethering and inhibit hyper-resection, and when these events are compromised, large deletions develop at a DSB. The work indicates that Nej1 provides a layer of regulation to repair pathway choice and is consistent with its role in NHEJ. Mojumdar et al. characterize the role of Nej1 during double-strand break repair. They show Nej1 promotes non-homologous end joining (NHEJ) by tethering the broken DNA ends and by inhibiting hyper-resection mediated by Dna2-Sgs1. © 2019 The Author(s) |
| Keywords: | dsb repair; nhej; 5′ resection; end-tethering; mre11-rad50-xrs2; mrx; nej1 |
| Journal Title: | Cell Reports |
| Volume: | 28 |
| Issue: | 6 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2019-08-06 |
| Start Page: | 1564 |
| End Page: | 1573.e3 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2019.07.018 |
| PROVIDER: | scopus |
| PUBMED: | 31390569 |
| PMCID: | PMC6746346 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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