Molecular basis for the regulation of the SUMOylation activity of the Smc5/6 complex by Esc2
Year: 2026
Type: article
Abstract: Post-translational modification by SUMO regulates a wide array of cellular processes. Despite the large number of SUMOylated substrates, only a limited set of SUMO E3 ligases have been identified, raising important questions about how substrate specificity is achieved. In budding yeast, the nuclear protein Esc2 functions as a cofactor in the SUMO pathway through its interaction with the E2 enzyme Ubc9. Esc2 is relevant under conditions of replicative stress, promoting the removal of recombination intermediates during DNA replication. This role has been largely attributed to its ability to enhance the SUMO E3 ligase activity of Nse2, a subunit of the Smc5/6 complex. Here, we uncover the molecular mechanism underlying Esc2-mediated stimulation of Nse2-dependent SUMOylation by identifying a direct interaction between the C-terminal SUMO-interacting motif of Nse2 and the Esc2 SLD2 domain. These coordinated interactions facilitate the formation of a productive E3-E2~SUMO complex and promote efficient SUMO transfer to substrates such as Sgs1 and Top3, thereby enhancing the processing of recombination intermediates and contributing to genome integrity. Esc2 promotes Nse2-dependent SUMOylation by directly binding Nse2 through its SLD2 domain. This interaction stabilizes a productive E3–E2~SUMO complex, enhances SUMO transfer to substrates such as Sgs1 and Top3, and preserves genome integrity.
Source: Communications Biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Centres de Recerca de Catalunya, European Commission, University of Sheffield, Generalitat de Catalunya, Institució Catalana de Recerca i Estudis Avançats, Ministerio de Ciencia e Innovación, Universitat de Lleida, Biotechnology and Biological Sciences Research Council, Agencia Estatal de Investigación
Awards: G1175115578, G1577046871, G1855990336, G2064873908, G2262748287, G2309174360, G2462415295, G2601397997, G2660406951, G3005324705, G300979063, G3275705967, G3293243049, G3480869486, G3518538256, G3546882995, G3681454997, G3746636746, Upgrade to 600 MHz NMR spectrometer, G4042783231, G425668148, G430777504, G480866104, G5080475149, G5195188938, G5403136496, G5421974903, G5806516646, G5842359595, G6656126374, G7084143925, G7434936867, G7466406081, G7609524924, G7736885172, G8089423575, G99296377
OpenAlex ID: W7204124198
FWCI:
Cites:
Cited by:
Related to: