SUMO-mediated recruitment allows timely function of the Yen1 nuclease in mitotic cells

The post-translational modification of DNA damage response proteins with SUMO is an important mechanism to orchestrate a timely and orderly recruitment of repair factors to damage sites. After DNA replication stress and double-strand break formation, a number of repair factors are SUMOylated and int...

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Bibliographic Details
Published in:PLoS genetics 2022-03, Vol.18 (3), p.e1009860-e1009860
Main Authors: Dorison, Hugo, Talhaoui, Ibtissam, Mazón, Gerard
Format: Article
Language:English
Subjects:
Amino acids
Biology and life sciences
Chromatids
Chromosome Segregation - genetics
Chromosomes
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA damage
DNA repair
DNA Repair - genetics
Double-strand break repair
Endonucleases - genetics
Enzymes
Genetic aspects
Genetic research
Genomes
Genomic instability
Genomic Instability - genetics
Holliday Junction Resolvases - genetics
Homologous recombination
Humans
Intermediates
Life Sciences
Localization
Mitosis
Mutation
Nuclease
Nucleases
Phosphorylation
Physical Sciences
Post-translation
Post-translational modification
Proteins
Research and Analysis Methods
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - genetics
Sister chromatids
Small Ubiquitin-Related Modifier Proteins - genetics
Small Ubiquitin-Related Modifier Proteins - metabolism
Yeast
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Description
Summary:The post-translational modification of DNA damage response proteins with SUMO is an important mechanism to orchestrate a timely and orderly recruitment of repair factors to damage sites. After DNA replication stress and double-strand break formation, a number of repair factors are SUMOylated and interact with other SUMOylated factors, including the Yen1 nuclease. Yen1 plays a critical role in ensuring genome stability and unperturbed chromosome segregation by removing covalently linked DNA intermediates between sister chromatids that are formed by homologous recombination. Here we show how this important role of Yen1 depends on interactions mediated by non-covalent binding to SUMOylated partners. Mutations in the motifs that allow SUMO-mediated recruitment of Yen1 impair its ability to resolve DNA intermediates and result in chromosome mis-segregation and increased genome instability.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1009860