Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection
- 1Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland;
- 2Department of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich 8093, Switzerland
- Corresponding author: petr.cejka{at}irb.usi.ch
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↵3 These authors contributed equally to this work.
Abstract
DNA double-strand break repair by homologous recombination is initiated by DNA end resection, which is commenced by the Mre11–Rad50–Xrs2 complex and Sae2 in yeast. Here we report that the nonhomologous end joining factor Ku limits the exonuclease activity of Mre11 and promotes its endonuclease to cleave 5′-terminated DNA strands at break sites. Following initial endonucleolytic cleavage past the obstacle, Exo1 specifically extends the resection track, leading to the generation of long 3′ overhangs that are required for homologous recombination. These experiments provide mechanistic insights into how short-range and long-range DNA end resection enzymes overcome obstacles near broken DNA ends to initiate recombination.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.308254.117.
- Received October 13, 2017.
- Accepted December 7, 2017.
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