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Cell Rep. 2016 May 10;15(6):1254-65. doi: 10.1016/j.celrep.2016.04.017. Epub 2016 Apr 28.

Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression.

Author information

1
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
2
University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN 55455, USA.
3
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: bieli003@umn.edu.

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.

PMID:
27134171
PMCID:
PMC4864160
DOI:
10.1016/j.celrep.2016.04.017
[Indexed for MEDLINE]
Free PMC Article

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