ATPase-dependent control of the Mms21 SUMO ligase during DNA repair

PLoS Biology
Marcelino Bermúdez-LópezJordi Torres-Rosell

Abstract

Modification of proteins by SUMO is essential for the maintenance of genome integrity. During DNA replication, the Mms21-branch of the SUMO pathway counteracts recombination intermediates at damaged replication forks, thus facilitating sister chromatid disjunction. The Mms21 SUMO ligase docks to the arm region of the Smc5 protein in the Smc5/6 complex; together, they cooperate during recombinational DNA repair. Yet how the activity of the SUMO ligase is controlled remains unknown. Here we show that the SUMO ligase and the chromosome disjunction functions of Mms21 depend on its docking to an intact and active Smc5/6 complex, indicating that the Smc5/6-Mms21 complex operates as a large SUMO ligase in vivo. In spite of the physical distance separating the E3 and the nucleotide-binding domains in Smc5/6, Mms21-dependent sumoylation requires binding of ATP to Smc5, a step that is part of the ligase mechanism that assists Ubc9 function. The communication is enabled by the presence of a conserved disruption in the coiled coil domain of Smc5, pointing to potential conformational changes for SUMO ligase activation. In accordance, scanning force microscopy of the Smc5-Mms21 heterodimer shows that the molecule is physically remodeled in a...Continue Reading

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Citations

Jun 1, 2016·Frontiers in Genetics·Néstor García-RodríguezHelle D Ulrich
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Apr 1, 2021·Molecular Biology of the Cell·Amanda I BradleyRichard G Gardner

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Methods Mentioned

BETA
sumoylation
immunoprecipitation
Fluorescence-Activated Cell Sorting
pull-down
FACS
pull down
two-hybrid
PCR
pull downs
co-immunoprecipitation

Software Mentioned

Image Lab
MATLAB
Image J

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