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J Cell Biol. 2019 Apr 1;218(4):1164-1181. doi: 10.1083/jcb.201806057. Epub 2019 Feb 14.

CDK1-mediated phosphorylation at H2B serine 6 is required for mitotic chromosome segregation.

Author information

1
Institute of Biochemistry, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.
2
Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
3
Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
4
Cell Division Biology Research Group, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, England, UK.
5
Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, and Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
6
Department of Pathology, Josephine Nefkens Institute, Erasmus Optical Imaging Centre, Erasmus MC, Rotterdam, Netherlands.
7
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
8
Department of Cell Biology and Cell Pathology, Philipps University of Marburg, Marburg, Germany.
9
Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany.
10
Institute of Biochemistry, Justus-Liebig-University, Member of the German Center for Lung Research, Giessen, Germany lienhard.schmitz@biochemie.med.uni-giessen.de.

Abstract

Faithful mitotic chromosome segregation is required for the maintenance of genomic stability. We discovered the phosphorylation of histone H2B at serine 6 (H2B S6ph) as a new chromatin modification site and found that this modification occurs during the early mitotic phases at inner centromeres and pericentromeric heterochromatin. This modification is directly mediated by cyclin B1-associated CDK1, and indirectly by Aurora B, and is antagonized by PP1-mediated dephosphorylation. H2B S6ph impairs chromatin binding of the histone chaperone SET (I2PP2A), which is important for mitotic fidelity. Injection of phosphorylation-specific H2B S6 antibodies in mitotic cells caused anaphase defects with impaired chromosome segregation and incomplete cytokinesis. As H2B S6ph is important for faithful chromosome separation, this modification may contribute to the prevention chromosomal instability and aneuploidy which frequently occur in cancer cells.

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