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


Proper repair of DNA lesions is crucial for cell growth and organism development. Both the choice and capacity of DNA repair pathways are tightly regulated in response to environmental cues and cell cycle phase. Recent work has uncovered the importance of protein modifications, such as phosphorylation and sumoylation, in this regulation. Sumoylation is known to be critical for the efficient repair of highly toxic DNA double-strand breaks in both yeast and humans, and this is partly mediated by influencing DNA end resection. However, it has been unclear for which resection factor sumoylation is important, how sumoylation influences specific attributes of the relevant targets, and how this modification is coordinated with phosphorylation-based regulation. Here, we provide exciting new insights into these issues by revealing that 1) a conserved end resection factor is a SUMO target relevant to this process, 2) this regulation favors a specific repair pathway, 3) sumoylation collaborates with phosphorylation to promote protein solubility, and 4) sumoylation influences DNA repair via an “ensemble effect” that entails simultaneous small alterations of multiple substrates. Our work reveals both a novel mechanism and a general principle for SUMO-mediated regulation of DNA repair.


Vyšlo v časopise: Sumoylation Influences DNA Break Repair Partly by Increasing the Solubility of a Conserved End Resection Protein. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004899
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004899

Souhrn

Proper repair of DNA lesions is crucial for cell growth and organism development. Both the choice and capacity of DNA repair pathways are tightly regulated in response to environmental cues and cell cycle phase. Recent work has uncovered the importance of protein modifications, such as phosphorylation and sumoylation, in this regulation. Sumoylation is known to be critical for the efficient repair of highly toxic DNA double-strand breaks in both yeast and humans, and this is partly mediated by influencing DNA end resection. However, it has been unclear for which resection factor sumoylation is important, how sumoylation influences specific attributes of the relevant targets, and how this modification is coordinated with phosphorylation-based regulation. Here, we provide exciting new insights into these issues by revealing that 1) a conserved end resection factor is a SUMO target relevant to this process, 2) this regulation favors a specific repair pathway, 3) sumoylation collaborates with phosphorylation to promote protein solubility, and 4) sumoylation influences DNA repair via an “ensemble effect” that entails simultaneous small alterations of multiple substrates. Our work reveals both a novel mechanism and a general principle for SUMO-mediated regulation of DNA repair.


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