A Failsafe for Sensing Chromatid Tension in Mitosis with the Histone H3 Tail in Saccharomyces cerevisiae.

Abstract:

:Mitotic fidelity is ensured by achieving biorientation on all paired chromosomes. The key signal for proper chromosome alignment is the tension between sister chromatids created by opposing poleward force from the spindles. In the budding yeast, the tension-sensing function requires that the Shugoshin protein, Shugoshin 1, be recruited to the centromeres and the neighboring pericentric regions. Concerted actions integrating proteins at centromeres and pericentromeres create highly specific Shugoshin 1 domains on mitotic chromosomes. We have previously reported that an important regulatory region on histone H3, termed the tension-sensing motif (TSM), is responsible for retaining Shugoshin 1 at pericentromeres. The TSM is negatively regulated by the acetyltransferase Gcn5p, but the underlying mechanism was elusive. In this work, we provide evidence that, when the TSM function is impaired, the histone H3 tail adopts a role that complements the damaged TSM to ensure faithful mitosis. This novel function of the H3 tail is controlled by Gcn5p, which targets selective lysine residues. Mutations to K14 and K23 ameliorate the mitotic defects resulting from TSM mutations. The restoration of faithful segregation is accompanied by regaining Shugoshin 1 access to the pericentric regions. Our data reveal a novel pathway for mitotic Shugoshin 1 recruitment and further reinforce the active role played by chromatins during their segregation in mitosis.

journal_name

Genetics

journal_title

Genetics

authors

Buehl CJ,Deng X,Luo J,Buranasudja V,Hazbun T,Kuo MH

doi

10.1534/genetics.117.300606

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

565-578

issue

2

eissn

0016-6731

issn

1943-2631

pii

genetics.117.300606

journal_volume

208

pub_type

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