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Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease
The SLX1-SLX4 endonuclease required for homologous recombination and DNA repair in eukaryotic cells cleaves a variety of branched DNA structures. The nuclease subunit SLX1 is activated by association with a scaffolding protein SLX4. At the present time, little is known about the structure of SLX1-SL...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407285/ https://www.ncbi.nlm.nih.gov/pubmed/25753413 http://dx.doi.org/10.1016/j.celrep.2015.02.019 |
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author | Gaur, Vineet Wyatt, Haley D.M. Komorowska, Weronika Szczepanowski, Roman H. de Sanctis, Daniele Gorecka, Karolina M. West, Stephen C. Nowotny, Marcin |
author_facet | Gaur, Vineet Wyatt, Haley D.M. Komorowska, Weronika Szczepanowski, Roman H. de Sanctis, Daniele Gorecka, Karolina M. West, Stephen C. Nowotny, Marcin |
author_sort | Gaur, Vineet |
collection | PubMed |
description | The SLX1-SLX4 endonuclease required for homologous recombination and DNA repair in eukaryotic cells cleaves a variety of branched DNA structures. The nuclease subunit SLX1 is activated by association with a scaffolding protein SLX4. At the present time, little is known about the structure of SLX1-SLX4 or its mechanism of action. Here, we report the structural insights into SLX1-SLX4 by detailing the crystal structure of Candida glabrata (Cg) Slx1 alone and in combination with the C-terminal region of Slx4. The structure of Slx1 reveals a compact arrangement of the GIY-YIG nuclease and RING domains, which is reinforced by a long α helix. Slx1 forms a stable homodimer that blocks its active site. Slx1-Slx4 interaction is mutually exclusive with Slx1 homodimerization, suggesting a mechanism for Slx1 activation by Slx4. |
format | Online Article Text |
id | pubmed-4407285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44072852015-04-26 Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease Gaur, Vineet Wyatt, Haley D.M. Komorowska, Weronika Szczepanowski, Roman H. de Sanctis, Daniele Gorecka, Karolina M. West, Stephen C. Nowotny, Marcin Cell Rep Report The SLX1-SLX4 endonuclease required for homologous recombination and DNA repair in eukaryotic cells cleaves a variety of branched DNA structures. The nuclease subunit SLX1 is activated by association with a scaffolding protein SLX4. At the present time, little is known about the structure of SLX1-SLX4 or its mechanism of action. Here, we report the structural insights into SLX1-SLX4 by detailing the crystal structure of Candida glabrata (Cg) Slx1 alone and in combination with the C-terminal region of Slx4. The structure of Slx1 reveals a compact arrangement of the GIY-YIG nuclease and RING domains, which is reinforced by a long α helix. Slx1 forms a stable homodimer that blocks its active site. Slx1-Slx4 interaction is mutually exclusive with Slx1 homodimerization, suggesting a mechanism for Slx1 activation by Slx4. Cell Press 2015-03-05 /pmc/articles/PMC4407285/ /pubmed/25753413 http://dx.doi.org/10.1016/j.celrep.2015.02.019 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Report Gaur, Vineet Wyatt, Haley D.M. Komorowska, Weronika Szczepanowski, Roman H. de Sanctis, Daniele Gorecka, Karolina M. West, Stephen C. Nowotny, Marcin Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease |
title | Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease |
title_full | Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease |
title_fullStr | Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease |
title_full_unstemmed | Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease |
title_short | Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease |
title_sort | structural and mechanistic analysis of the slx1-slx4 endonuclease |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407285/ https://www.ncbi.nlm.nih.gov/pubmed/25753413 http://dx.doi.org/10.1016/j.celrep.2015.02.019 |
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