DNA activates the Nse2/Mms21 SUMO E3 ligase in the Smc5/6 complex

The EMBO Journal
Nathalia VarejãoDavid Reverter

Abstract

Modification of chromosomal proteins by conjugation to SUMO is a key step to cope with DNA damage and to maintain the integrity of the genome. The recruitment of SUMO E3 ligases to chromatin may represent one layer of control on protein sumoylation. However, we currently do not understand how cells upregulate the activity of E3 ligases on chromatin. Here we show that the Nse2 SUMO E3 in the Smc5/6 complex, a critical player during recombinational DNA repair, is directly stimulated by binding to DNA Activation of sumoylation requires the electrostatic interaction between DNA and a positively charged patch in the ARM domain of Smc5, which acts as a DNA sensor that subsequently promotes a stimulatory activation of the E3 activity in Nse2. Specific disruption of the interaction between the ARM of Smc5 and DNA sensitizes cells to DNA damage, indicating that this mechanism contributes to DNA repair. These results reveal a mechanism to enhance a SUMO E3 ligase activity by direct DNA binding and to restrict sumoylation in the vicinity of those Smc5/6-Nse2 molecules engaged on DNA.

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Citations

Oct 24, 2018·Molecular and Cellular Biology·Martina OravcováMichael N Boddy
May 26, 2018·The EMBO Journal·Andrea Pichler
Dec 25, 2019·Biochemical Society Transactions·Nathalia VarejãoDavid Reverter
Sep 24, 2020·Biochemical Society Transactions·Roger Solé-Soler, Jordi Torres-Rosell
Jan 31, 2020·Frontiers in Cell and Developmental Biology·Jan Keiten-SchmitzStefan Müller
Jan 3, 2019·Current Genetics·Martina Oravcová, Michael N Boddy
Dec 26, 2018·Genes·Jan J Palecek
Jan 22, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Wenhui LiuNian Fu
Dec 11, 2020·Molecular Cell·Pilar Gutierrez-EscribanoLuis Aragon
Apr 27, 2021·Frontiers in Plant Science·Souleimen Jmii, Laurent Cappadocia
Jul 1, 2021·The EMBO Journal·Michael TaschnerStephan Gruber
Jul 24, 2018·Molecular Pharmaceutics·Marcos Gil-GarciaSalvador Ventura
Aug 27, 2021·Journal of Molecular Biology·Fatéma DodatDaniel Lévesque
Sep 30, 2021·The EMBO Journal·Laurent CappadociaChristopher D Lima

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