Phosphorylation by CK2 regulates MUS81/EME1 in mitosis and after replication stress

Nucleic Acids Research
Anita PalmaPietro Pichierri

Abstract

The MUS81 complex is crucial for preserving genome stability through the resolution of branched DNA intermediates in mitosis. However, untimely activation of the MUS81 complex in S-phase is dangerous. Little is known about the regulation of the human MUS81 complex and how deregulated activation affects chromosome integrity. Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex. In line with a role in mitosis, phosphorylation at Serine 87 is suppressed in S-phase and is mainly detected in the MUS81 molecules associated with EME1. Loss of CK2-dependent MUS81 phosphorylation contributes modestly to chromosome integrity, however, expression of the phosphomimic form induces DSBs accumulation in S-phase, because of unscheduled targeting of HJ-like DNA intermediates, and generates a wide chromosome instability phenotype. Collectively, our findings describe a novel regulatory mechanism controlling the MUS81 complex function in human cells. Furthermore, they indicate that, genome stability depends mainly on the ability of cells to counteract targeting of branched in...Continue Reading

Citations

Dec 19, 2018·Genes·Seong Min Kim, Susan L Forsburg
Sep 12, 2020·Seminars in Cell & Developmental Biology·Jonas BaggeMichael Lisby
Jun 12, 2021·Royal Society Open Science·Camelia Mocanu, Kok-Lung Chan
Jul 31, 2021·Current Opinion in Genetics & Development·Antoine Simoneau, Lee Zou
Aug 28, 2021·Biomolecules·Commodore St GermainJacqueline H Barlow

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Methods Mentioned

BETA
transfection
immunoprecipitation
Fluorescence
flow cytometry
co-immunoprecipitation
proximity-ligation assay
CoIP
chromosomal aberrations

Software Mentioned

Photoshop
PLA
Image Lab

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