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

Varejao, Nathalia; Ibars Estiarte, Eva Irene; Lascorz, Jara; Colomina i Gabarrella, Neus; Torres Rosell, Jordi; Reverter Cendrós, David

doi:https://doi.org/10.15252/embj.201798306

View/Open

028543.pdf (8.338Mb)

Issue date

2018-06-15

Author

Varejao, Nathalia

Ibars Estiarte, Eva Irene

Lascorz, Jara

Colomina i Gabarrella, Neus

Torres Rosell, Jordi

Reverter Cendrós, David

Suggested citation

Varejao, Nathalia; Ibars Estiarte, Eva Irene; Lascorz, Jara; Colomina i Gabarrella, Neus; Torres Rosell, Jordi; Reverter Cendrós, David; . (2018) . DNA activates the Nse2/Mms21 SUMO E3 ligase in the Smc5/6 complex. Embo Journal, 2018, vol. 37, núm. 12. https://doi.org/10.15252/embj.201798306.

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.

URI

http://hdl.handle.net/10459.1/67685

DOI

https://doi.org/10.15252/embj.201798306

Is part of

Embo Journal, 2018, vol. 37, núm. 12