2026-06-14T05:06:08Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/191902024-11-29T18:08:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Jacome, Ariana
author
Gutierrez-Martinez, Paula
author
Schiavoni, Federica
author
Tenaglia, Enrico
author
Martinez, Paula
author
Rodríguez-Acebes, Sara
author
Lecona, Emilio
author
Murga, Matilde
author
Mendez, Juan
author
Blasco, MA
author
Fernandez-Capetillo, Oscar
funder
Fundacion Botin
funder
Banco Santander
funder
Howard Hughes Medical Institute
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Worldwide Cancer Research
funder
Ministerio de Ciencia e Innovación (España)
2024-04-24T05:49:23Z
2024-04-24T05:49:23Z
2015-11-03
EMBO J . 2015 3;34(21):2604-19
10.15252/embj.201591829
1460-2075
The EMBO journal
26443207
http://hdl.handle.net/20.500.12105/19190
The SMC5/6 complex is the least understood of SMC complexes. In yeast, smc5/6 mutants phenocopy mutations in sgs1, the BLM ortholog that is deficient in Bloom's syndrome (BS). We here show that NSMCE2 (Mms21, in Saccharomyces cerevisiae), an essential SUMO ligase of the SMC5/6 complex, suppresses cancer and aging in mice. Surprisingly, a mutation that compromises NSMCE2-dependent SUMOylation does not have a detectable impact on murine lifespan. In contrast, NSMCE2 deletion in adult mice leads to pathologies resembling those found in patients of BS. Moreover, and whereas NSMCE2 deletion does not have a detectable impact on DNA replication, NSMCE2-deficient cells also present the cellular hallmarks of BS such as increased recombination rates and an accumulation of micronuclei. Despite the similarities, NSMCE2 and BLM foci do not colocalize and concomitant deletion of Blm and Nsmce2 in B lymphocytes further increases recombination rates and is synthetic lethal due to severe chromosome mis-segregation. Our work reveals that SUMO- and BLM-independent activities of NSMCE2 limit recombination and facilitate segregation; functions of the SMC5/6 complex that are necessary to prevent cancer and aging in mice.
eng
NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.
journal article
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