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Journal of Hematology & Oncology

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Open Access 01-12-2016 | Research

Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence

Authors: Sung-Hyun Park, Steve Xie, Chinthalapally V. Rao, Wei Dai

Published in: Journal of Hematology & Oncology | Issue 1/2016

Abstract

Background

Spindle assembly checkpoint components BubR1 and Sgo1 play a key role in the maintenance of chromosomal instability during cell division. These proteins function to block the anaphase entry until all condensed chromosomes have been attached by the microtubules emanating from both spindle poles. Haplo-insufficiency of either BubR1 or SGO1 results in enhanced chromosomal instability and tumor development in the intestine. Recent studies show that spindle checkpoint proteins also have a role in slowing down the ageing process. Therefore, we want to study whether haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence in mice.

Methods

We took advantage of the availability of BubR1 and SGO1 knockout mice and generated primary murine embryonic fibroblasts (MEFs) with mutations in either BubR1, SGO1, or both and analyzed cellular senescence of the MEFs of various genetic backgrounds.

Results

We observed that BubR1 ^+/− SGO ^+/− MEFs had an accelerated cellular senescence characterized by morphological changes and expressed senescence-associated β-galactosidase. In addition, compared with wild-type MEFs or MEFs with a single gene deficiency, BubR1 ^+/− SGO1 ^+/− MEFs expressed enhanced levels of p21 but not p16.

Conclusions

Taken together, our observations suggest that combined deficiency of BubR1 and Sgo1 accelerates cellular senescence.

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Title: Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence
Authors: Sung-Hyun Park
Steve Xie
Chinthalapally V. Rao
Wei Dai
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2016
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-016-0238-5

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