Reference: Zapatka M, et al. (2019) Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks. Cell Rep 29(10):3160-3172.e4

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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 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.

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Journal Article | Research Support, Non-U.S. Gov't
Authors
Zapatka M, Pociño-Merino I, Heluani-Gahete H, Bermúdez-López M, Tarrés M, Ibars E, Solé-Soler R, Gutiérrez-Escribano P, Apostolova S, Casas C, ... Show all
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