Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein

Protein modifications regulate both DNA repair levels and pathway choice. How each modification achieves regulatory effects and how different modifications collaborate with each other are important questions to be answered. Here, we show that sumoylation regulates double-strand break repair partly b...

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Main Authors:	Sarangi, Prabha, Steinacher, Roland, Altmannova, Veronika, Fu, Qiong, Paull, Tanya T., Krejci, Lumir, Whitby, Matthew C., Zhao, Xiaolan
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287433/

id	pubmed-4287433
recordtype	oai_dc
spelling	pubmed-42874332015-01-12 Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein Sarangi, Prabha Steinacher, Roland Altmannova, Veronika Fu, Qiong Paull, Tanya T. Krejci, Lumir Whitby, Matthew C. Zhao, Xiaolan Research Article Protein modifications regulate both DNA repair levels and pathway choice. How each modification achieves regulatory effects and how different modifications collaborate with each other are important questions to be answered. Here, we show that sumoylation regulates double-strand break repair partly by modifying the end resection factor Sae2. This modification is conserved from yeast to humans, and is induced by DNA damage. We mapped the sumoylation site of Sae2 to a single lysine in its self-association domain. Abolishing Sae2 sumoylation by mutating this lysine to arginine impaired Sae2 function in the processing and repair of multiple types of DNA breaks. We found that Sae2 sumoylation occurs independently of its phosphorylation, and the two modifications act in synergy to increase soluble forms of Sae2. We also provide evidence that sumoylation of the Sae2-binding nuclease, the Mre11-Rad50-Xrs2 complex, further increases end resection. These findings reveal a novel role for sumoylation in DNA repair by regulating the solubility of an end resection factor. They also show that collaboration between different modifications and among multiple substrates leads to a stronger biological effect. Public Library of Science 2015-01-08 /pmc/articles/PMC4287433/ /pubmed/25569253 http://dx.doi.org/10.1371/journal.pgen.1004899 Text en © 2015 Sarangi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sarangi, Prabha Steinacher, Roland Altmannova, Veronika Fu, Qiong Paull, Tanya T. Krejci, Lumir Whitby, Matthew C. Zhao, Xiaolan
spellingShingle	Sarangi, Prabha Steinacher, Roland Altmannova, Veronika Fu, Qiong Paull, Tanya T. Krejci, Lumir Whitby, Matthew C. Zhao, Xiaolan Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein
author_facet	Sarangi, Prabha Steinacher, Roland Altmannova, Veronika Fu, Qiong Paull, Tanya T. Krejci, Lumir Whitby, Matthew C. Zhao, Xiaolan
author_sort	Sarangi, Prabha
title	Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein
title_short	Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein
title_full	Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein
title_fullStr	Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein
title_full_unstemmed	Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein
title_sort	sumoylation influences dna break repair partly by increasing the solubility of a conserved end resection protein
description	Protein modifications regulate both DNA repair levels and pathway choice. How each modification achieves regulatory effects and how different modifications collaborate with each other are important questions to be answered. Here, we show that sumoylation regulates double-strand break repair partly by modifying the end resection factor Sae2. This modification is conserved from yeast to humans, and is induced by DNA damage. We mapped the sumoylation site of Sae2 to a single lysine in its self-association domain. Abolishing Sae2 sumoylation by mutating this lysine to arginine impaired Sae2 function in the processing and repair of multiple types of DNA breaks. We found that Sae2 sumoylation occurs independently of its phosphorylation, and the two modifications act in synergy to increase soluble forms of Sae2. We also provide evidence that sumoylation of the Sae2-binding nuclease, the Mre11-Rad50-Xrs2 complex, further increases end resection. These findings reveal a novel role for sumoylation in DNA repair by regulating the solubility of an end resection factor. They also show that collaboration between different modifications and among multiple substrates leads to a stronger biological effect.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287433/
_version_	1613174300036038656

Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein

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