2026-06-14T03:37:27Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/191902024-11-29T18:08:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2015-11-03 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. 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 NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.