Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 May 3

PMID 27134171

Citations 29

Authors

Yee Mon Thu

Susan Kaye Van Riper

LeeAnn Higgins

Tianji Zhang

Jordan Robert Becker

Todd William Markowski

Hai Dang Nguyen

Timothy Jon Griffin

Anja Katrin Bielinsky

Affiliations

Soon will be listed here.

Abstract

Loss of minichromosome maintenance protein 10 (Mcm10) causes replication stress. We uncovered that S. cerevisiae mcm10-1 mutants rely on the E3 SUMO ligase Mms21 and the SUMO-targeted ubiquitin ligase complex Slx5/8 for survival. Using quantitative mass spectrometry, we identified changes in the SUMO proteome of mcm10-1 mutants and revealed candidates regulated by Slx5/8. Such candidates included subunits of the chromosome passenger complex (CPC), Bir1 and Sli15, known to facilitate spindle assembly checkpoint (SAC) activation. We show here that Slx5 counteracts SAC activation in mcm10-1 mutants under conditions of moderate replication stress. This coincides with the proteasomal degradation of sumoylated Bir1. Importantly, Slx5-dependent mitotic relief was triggered not only by Mcm10 deficiency but also by treatment with low doses of the alkylating drug methyl methanesulfonate. Based on these findings, we propose a model in which Slx5/8 allows for passage through mitosis when replication stress is tolerable.

Citing Articles

The fission yeast SUMO-targeted ubiquitin ligase Slx8 functionally associates with clustered centromeres and the silent mating-type region at the nuclear periphery.

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Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.

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Multifaceted roles of SUMO in DNA metabolism.

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Restricting the level of the proteins essential for the regulation of the initiation step of replication extends the chronological lifespan and reproductive potential in budding yeast.

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