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Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection
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 cl...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795779/ https://www.ncbi.nlm.nih.gov/pubmed/29321179 http://dx.doi.org/10.1101/gad.308254.117 |
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author | Reginato, Giordano Cannavo, Elda Cejka, Petr |
author_facet | Reginato, Giordano Cannavo, Elda Cejka, Petr |
author_sort | Reginato, Giordano |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5795779 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57957792018-06-01 Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection Reginato, Giordano Cannavo, Elda Cejka, Petr Genes Dev Research Communication 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. Cold Spring Harbor Laboratory Press 2017-12-01 /pmc/articles/PMC5795779/ /pubmed/29321179 http://dx.doi.org/10.1101/gad.308254.117 Text en © 2018 Reginato et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Communication Reginato, Giordano Cannavo, Elda Cejka, Petr Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection |
title | Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection |
title_full | Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection |
title_fullStr | Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection |
title_full_unstemmed | Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection |
title_short | Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection |
title_sort | physiological protein blocks direct the mre11–rad50–xrs2 and sae2 nuclease complex to initiate dna end resection |
topic | Research Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795779/ https://www.ncbi.nlm.nih.gov/pubmed/29321179 http://dx.doi.org/10.1101/gad.308254.117 |
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