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Mutations that prevent methylation of cohesin render sensitivity to DNA damage in S. pombe

The canonical role of cohesin is to mediate sister chromatid cohesion. In addition, cohesin plays important roles in processes such as DNA repair and regulation of gene expression. Mounting evidence suggests that various post-translational modifications, including phosphorylation, acetylation and su...

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Detalles Bibliográficos
Autores principales: Sanyal, Swastika, Molnarova, Lucia, Richterova, Judita, Huraiova, Barbora, Benko, Zsigmond, Polakova, Silvia, Cipakova, Ingrid, Sevcovicova, Andrea, Gaplovska-Kysela, Katarina, Mechtler, Karl, Cipak, Lubos, Gregan, Juraj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051343/
https://www.ncbi.nlm.nih.gov/pubmed/29898918
http://dx.doi.org/10.1242/jcs.214924
Descripción
Sumario:The canonical role of cohesin is to mediate sister chromatid cohesion. In addition, cohesin plays important roles in processes such as DNA repair and regulation of gene expression. Mounting evidence suggests that various post-translational modifications, including phosphorylation, acetylation and sumoylation regulate cohesin functions. Our mass spectrometry analysis of cohesin purified from Schizosaccharomyces pombe cells revealed that the cohesin subunit Psm1 is methylated on two evolutionarily conserved lysine residues, K536 and K1200. We found that mutations that prevent methylation of Psm1 K536 and K1200 render sensitivity to DNA-damaging agents and show positive genetic interactions with mutations in genes encoding the Mus81–Eme1 endonuclease. Yeast two-hybrid and co-immunoprecipitation assays showed that there were interactions between subunits of the cohesin and Mus81–Eme1 complexes. We conclude that cohesin is methylated and that mutations that prevent methylation of Psm1 K536 and K1200 show synthetic phenotypes with mutants defective in the homologous recombination DNA repair pathway.