Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis.

TitleAurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis.
Publication TypeJournal Article
Year of Publication2016
AuthorsWike CL, Graves HK, Hawkins R, Gibson MD, Ferdinand MB, Zhang T, Chen Z, Hudson DF, Ottesen JJ, Poirier MG, Schumacher J, Tyler JK
JournalElife
Volume5
Paginatione11402
Date Published2016 Feb 16
ISSN2050-084X
KeywordsAdenosine Triphosphatases, Animals, Aurora Kinase A, Cell Cycle Proteins, Cell Line, Chromosomal Proteins, Non-Histone, DNA, DNA-Binding Proteins, Drosophila, Histones, Humans, Mitosis, Multiprotein Complexes, Phosphorylation, Protein Processing, Post-Translational, Threonine
Abstract

Phosphorylation of histone H3 threonine 118 (H3 T118ph) weakens histone DNA-contacts, disrupting the nucleosome structure. We show that Aurora-A mediated H3 T118ph occurs at pericentromeres and chromosome arms during prophase and is lost upon chromosome alignment. Expression of H3 T118E or H3 T118I (a SIN mutation that bypasses the need for the ATP-dependent nucleosome remodeler SWI/SNF) leads to mitotic problems including defects in spindle attachment, delayed cytokinesis, reduced chromatin packaging, cohesion loss, cohesin and condensin I loss in human cells. In agreement, overexpression of Aurora-A leads to increased H3 T118ph levels, causing cohesion loss, and reduced levels of cohesin and condensin I on chromatin. Normal levels of H3 T118ph are important because it is required for development in fruit flies. We propose that H3 T118ph alters the chromatin structure during specific phases of mitosis to promote timely condensin I and cohesin disassociation, which is essential for effective chromosome segregation.

DOI10.7554/eLife.11402
Alternate JournalElife
PubMed ID26878753
PubMed Central IDPMC4798946
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
R01 GM083055 / GM / NIGMS NIH HHS / United States
R01 CA95641 / CA / NCI NIH HHS / United States
R01GM64475 / GM / NIGMS NIH HHS / United States
R01 GM064475 / GM / NIGMS NIH HHS / United States
Related Faculty: 
Jessica K. Tyler, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700