Open AccessMutations that prevent methylation of cohesin render sensitivity to DNA damage
Author(s) -
Swastika Sanyal,
Lucia Molnárová,
Judita Richterova,
Barbora Huraiová,
Zsigmond Benkő,
Silvia Poláková,
Ingrid Čipáková,
Andrea Ševčovičová,
Katarína Gaplovská-Kyselá,
Karl Mechtler,
Luboš Čipák,
Juraj Gregáň
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.214924
Subject(s) - cohesin , biology , establishment of sister chromatid cohesion , schizosaccharomyces pombe , genetics , dna repair , schizosaccharomyces , mutant , microbiology and biotechnology , dna , gene , chromatin
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.