Universität zu Köln

Seibert, Markus ORCID: 0000-0001-5708-4856, Kruger, Marcus, Watson, Nikolaus A., Sen, Onur ORCID: 0000-0002-6685-7010, Daum, John R., Slotman, Johan A. ORCID: 0000-0001-9705-9620, Braun, Thomas ORCID: 0000-0002-6165-4804, Houtsmuller, Adriaan B., Gorbsky, Gary J., Jacob, Ralf ORCID: 0000-0002-9251-6578, Kracht, Michael, Higgins, Jonathan M. G. and Schmitz, M. Lienhard ORCID: 0000-0002-6984-7192 (2019). CDK1-mediated phosphorylation at H2B serine 6 is required for mitotic chromosome segregation. J. Cell Biol., 218 (4). S. 1164 - 1182. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seibert, Markus UNSPECIFIED orcid.org/0000-0001-5708-4856 UNSPECIFIED Kruger, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Watson, Nikolaus A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sen, Onur UNSPECIFIED orcid.org/0000-0002-6685-7010 UNSPECIFIED Daum, John R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Slotman, Johan A. UNSPECIFIED orcid.org/0000-0001-9705-9620 UNSPECIFIED Braun, Thomas UNSPECIFIED orcid.org/0000-0002-6165-4804 UNSPECIFIED Houtsmuller, Adriaan B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gorbsky, Gary J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jacob, Ralf UNSPECIFIED orcid.org/0000-0002-9251-6578 UNSPECIFIED Kracht, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Higgins, Jonathan M. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, M. Lienhard UNSPECIFIED orcid.org/0000-0002-6984-7192 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-152643
DOI:	10.1083/jcb.201806057
Journal or Publication Title:	J. Cell Biol.
Volume:	218
Number:	4
Page Range:	S. 1164 - 1182
Date:	2019
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AURORA-B; HISTONE H3; CELL-CYCLE; THR-3 PHOSPHORYLATION; IDENTIFICATION; CDK1; METHYLATION; MITOSIS; KINASE; SET Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15264