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J Cell Sci. 2018 Jul 6;131(13). pii: jcs214924. doi: 10.1242/jcs.214924.

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

Author information

1
Department of Chromosome Biology, MFPL, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria.
2
Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 842 15 Bratislava, Slovakia.
3
Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, 84505 Bratislava, Slovakia.
4
Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 84505 Bratislava, Slovakia.
5
Research Institute of Molecular Pathology, Campus-Vienna-Biocenter 1, 1030 Vienna, Austria.
6
Department of Chromosome Biology, MFPL, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria juraj.gregan@univie.ac.at.
7
Advanced Microscopy Facility, Vienna Biocenter Core Facilities, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.

Abstract

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.

KEYWORDS:

Cohesin; DNA repair; Meiosis; Mitosis; Schizosaccharomyces pombe

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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