Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
Pociño Merino, Irene
Heluani Gahete, Hayat
Bermúdez López, Marcelino
Solé Soler, Roger
Gutiérrez Escribano, Pilar
Wellinger, Ralf Erik
Torres Rosell, Jordi
|Department||Universidad de Sevilla. Departamento de Genética|
|Abstract||Replication 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 ...
Replication 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.
|Funding agencies||Ministerio de Ciencia, Innovación y Universidades (MICINN). España|
|Citation||Zapatka, M., Pociño Merino, I., Heluani Gahete, H., Bermúdez López, M., Tarrés, M., Ibars, E.,...,Torres Rosell, J. (2019). Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks. Cell Reports, 20 (10), 3160-3172.|