Zapatka, MarielPociño-Merino, IreneHeluani-Gahete, HayatBermúdez-López, MarcelinoTarrés, MarcIbars, EvaSolé-Soler, RogerGutiérrez-Escribano, PilarApostolova, SoniaCasas, CeliaAragon, LuisWellinger, RalfColomina, NeusTorres-Rosell, Jordi2023-02-082023-02-082019http://hdl.handle.net/10668/14788Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits within the Smc5/6 complex are substrates of Nse2, but we currently do not know the role of these modifications. Here we show that sumoylation of Smc5 is targeted to its coiled-coil domain, is upregulated by replication fork damage, and participates in bypass of DNA lesions. smc5-KR mutant cells display defects in formation of sister chromatid junctions and higher translesion synthesis. Also, we provide evidence indicating that Smc5 sumoylation modulates Mph1-dependent fork regression, acting synergistically with other pathways to promote chromosome disjunction. We propose that sumoylation of Smc5 enhances physical remodeling of damaged forks, avoiding the use of a more mutagenic tolerance pathway.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/DNA damage toleranceDNA replicationMms21Mph1Nse2SUMOSmc5chromosomefork regressionyeastCell Cycle ProteinsChromatidsChromosomesDNADNA DamageDNA RepairDNA ReplicationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSumoylationresearch article31801080open access10.1016/j.celrep.2019.10.1232211-1247http://www.cell.com/article/S2211124719314561/pdf