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Sumo-Directed Control of the Resolvase Yen1 in Mitotic Cells

Abstract : The repair of double-stranded DNA breaks (DSBs) by homologous recombination involves the formation of branched intermediates that can lead to crossovers following nucleolytic resolution. Ubiquitin and SUMO modification is commonplace amongst the DNA damage repair proteins. What is more, a number of DSB repair factors interact with each other when sumoylated, making use of SUMO interaction motifs (SIMs). The nuclease Yen1 is tightly controlled during the cell cycle to limit the extent of crossover formation and preserve genome integrity. In this manuscript we describe further regulation of Yen1 by ubiquitination, sumoylation and non-covalent interaction with SUMO through its newly characterized SIMs. Yen1 is sumoylated by Siz1 and Siz2 SUMO ligases, especially in conditions of DNA damage. Furthermore, Yen1 is a substrate of the Slx5-Slx8 ubiquitin ligase. Loss of Slx5-Slx8 stabilizes the sumoylated fraction of Yen1, and results in persistent localization of Yen1 in nuclear foci. Slx5-Slx8-dependent ubiquitination of Yen1 occurs mainly at K714 and mutation of this lysine increases crossover formation during DSB repair and suppresses chromosome segregation defects when other nucleases are unavailable. In addition, proper and timely nucleolytic processing from Yen1 is dependent on interactions mediated by non-covalent binding to sumoylated partners. Mutations in the motifs that allow SUMO-mediated recruitment of Yen1 leads to its mis-localization, decreasing Yen1’s ability to resolve DNA joint-molecule intermediates and resulting in increased genome instability and chromosome mis-segregation.
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Submitted on : Saturday, January 22, 2022 - 1:01:17 AM
Last modification on : Sunday, January 23, 2022 - 3:24:54 AM
Long-term archiving on: : Saturday, April 23, 2022 - 6:02:39 PM


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  • HAL Id : tel-03539739, version 1


Hugo Dorison. Sumo-Directed Control of the Resolvase Yen1 in Mitotic Cells. Genomics [q-bio.GN]. Université Paris-Saclay, 2021. English. ⟨NNT : 2021UPASL003⟩. ⟨tel-03539739⟩



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