Sumoylation influences DNA break repair partly by increasing the solubility of a conserved end resection protein Journal Article
| Authors: | Sarangi, P.; Steinacher, R.; Altmannova, V.; Fu, Q.; Paull, T. T.; Krejci, L.; Whitby, M. C.; Zhao, X. |
| Article Title: | Sumoylation influences DNA break repair partly by increasing the solubility of a conserved end resection protein |
| Abstract: | 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. © 2015 Sarangi et al. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; unclassified drug; nonhuman; binding affinity; protein function; mre11 protein; dna damage; complex formation; dna repair; cell protein; molecular dynamics; protein binding; dna strand breakage; nuclease; binding protein; binding site; sumoylation; protein determination; genetic conservation; lysine; arginine; protein rad9; solubility; peptide mapping; nucleic acid structure, metabolism and function; article; sae2 protein; xrs2 protein; dna end clipping |
| Journal Title: | PLoS Genetics |
| Volume: | 11 |
| Issue: | 1 |
| ISSN: | 1553-7390 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-01-08 |
| Start Page: | e1004899 |
| Language: | English |
| DOI: | 10.1371/journal.pgen.1004899 |
| PROVIDER: | scopus |
| PMCID: | PMC4287433 |
| PUBMED: | 25569253 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2015 -- Source: Scopus |
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