Format

Send to

Choose Destination
Mol Cell. 2017 Aug 17;67(4):579-593.e6. doi: 10.1016/j.molcel.2017.07.008. Epub 2017 Aug 3.

Phospho-H1 Decorates the Inter-chromatid Axis and Is Evicted along with Shugoshin by SET during Mitosis.

Author information

1
Howard Hughes Medical Institute, New York University Langone School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA.
2
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, 6525 GA Nijmegen, the Netherlands.
3
Howard Hughes Medical Institute, New York University Langone School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA. Electronic address: danny.reinberg@nyumc.org.

Abstract

Precise control of sister chromatid separation during mitosis is pivotal to maintaining genomic integrity. Yet, the regulatory mechanisms involved are not well understood. Remarkably, we discovered that linker histone H1 phosphorylated at S/T18 decorated the inter-chromatid axial DNA on mitotic chromosomes. Sister chromatid resolution during mitosis required the eviction of such H1S/T18ph by the chaperone SET, with this process being independent of and most likely downstream of arm-cohesin dissociation. SET also directed the disassembly of Shugoshins in a polo-like kinase 1-augmented manner, aiding centromere resolution. SET ablation compromised mitotic fidelity as evidenced by unresolved sister chromatids with marked accumulation of H1S/T18ph and centromeric Shugoshin. Thus, chaperone-assisted eviction of linker histones and Shugoshins is a fundamental step in mammalian mitotic progression. Our findings also elucidate the functional implications of the decades-old observation of mitotic linker histone phosphorylation, serving as a paradigm to explore the role of linker histones in bio-signaling processes.

KEYWORDS:

Shugoshin; chromatid resolution; chromosome integrity; histone H1; histone chaperone; linker histone; mitosis; phosphorylation

PMID:
28781233
PMCID:
PMC5562512
DOI:
10.1016/j.molcel.2017.07.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center