Oncotarget

Priority Research Papers:

Cell cycle regulation of condensin Smc4

Hsu Wei-Shan, Vas C. Amit, Duncan J. Clarke _

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Oncotarget. 2019; 10:263-276. https://doi.org/10.18632/oncotarget.26467

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Abstract

Hsu Wei-Shan1,*, Vas C. Amit1,2,* and Duncan J. Clarke1

1 Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, MN, USA

2 Present address: Cargill Inc., Wayzata, MN, USA

* Co-first authors

Correspondence to:

Duncan J. Clarke, email: clark140@umn.edu

Vas C. Amit, email: acjvas@gmail.com

Keywords: condensin; Smc4; Smc2; Mad2; anaphase promoting complex

Received: July 27, 2018    Accepted: December 04, 2018    Published: January 08, 2019

Abstract

The condensin complex is a conserved ATPase which promotes the compaction of chromatin during mitosis in eukaryotic cells. Condensin complexes have in addition been reported to contribute to interphase processes including sister chromatid cohesion. It is not understood how condensins specifically become competent to facilitate chromosome condensation in preparation for chromosome segregation in anaphase. Here we describe evidence that core condensin subunits are regulated at the level of protein stability in budding yeast. In particular, Smc2 and Smc4 abundance is cell cycle regulated, peaking at mitosis and falling to low levels in interphase. Smc4 degradation at the end of mitosis is dependent on the Anaphase Promoting Complex/Cyclosome and is mediated by the proteasome. Overproduction of Smc4 results in delayed decondensation, but has a limited ability to promote premature condensation in interphase. Unexpectedly, the Mad2 spindle checkpoint protein is required for mitotic Smc4 degradation. These studies have revealed the novel finding that condensin protein levels are cell cycle regulated and have identified the factors necessary for Smc4 proteolysis.


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