RT Journal Article
T1 Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks.
A1 Zapatka, Mariel
A1 Pociño-Merino, Irene
A1 Heluani-Gahete, Hayat
A1 Bermúdez-López, Marcelino
A1 Tarrés, Marc
A1 Ibars, Eva
A1 Solé-Soler, Roger
A1 Gutiérrez-Escribano, Pilar
A1 Apostolova, Sonia
A1 Casas, Celia
A1 Aragon, Luis
A1 Wellinger, Ralf
A1 Colomina, Neus
A1 Torres-Rosell, Jordi
K1 DNA damage tolerance
K1 DNA replication
K1 Mms21
K1 Mph1
K1 Nse2
K1 SUMO
K1 Smc5
K1 chromosome
K1 fork regression
K1 yeast
AB 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.
YR 2019
FD 2019
LK http://hdl.handle.net/10668/14788
UL http://hdl.handle.net/10668/14788
LA en
DS RISalud
RD Apr 7, 2025