2026-05-17T05:52:22Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/176572024-11-29T23:37:43Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Remeseiro, Silvia
author
Cuadrado, Ana
author
Carretero, María
author
Martínez, Paula
author
Drosopoulos, William C
author
Cañamero, Marta
author
Schildkraut, Carl L
author
Blasco, MA
author
Losada, Ana
funder
Ministerio de Ciencia e Innovación (España)
funder
Fundación La Caixa
funder
NIH - National Cancer Institute (NCI) (Estados Unidos)
2024-02-08T18:31:52Z
2024-02-08T18:31:52Z
2012-05-02
EMBO J . 2012;31(9):2076-89.
10.1038/emboj.2012.11
1460-2075
The EMBO journal
22415365
http://hdl.handle.net/20.500.12105/17657
Cohesin is a protein complex originally identified for its role in sister chromatid cohesion, although increasing evidence portrays it also as a major organizer of interphase chromatin. Vertebrate cohesin consists of Smc1, Smc3, Rad21/Scc1 and either stromal antigen 1 (SA1) or SA2. To explore the functional specificity of these two versions of cohesin and their relevance for embryonic development and cancer, we generated a mouse model deficient for SA1. Complete ablation of SA1 results in embryonic lethality, while heterozygous animals have shorter lifespan and earlier onset of tumourigenesis. SA1-null mouse embryonic fibroblasts show decreased proliferation and increased aneuploidy as a result of chromosome segregation defects. These defects are not caused by impaired centromeric cohesion, which depends on cohesin-SA2. Instead, they arise from defective telomere replication, which requires cohesion mediated specifically by cohesin-SA1. We propose a novel mechanism for aneuploidy generation that involves impaired telomere replication upon loss of cohesin-SA1, with clear implications in tumourigenesis.
eng
Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres.
journal article
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URL
https://repisalud.isciii.es/bitstreams/48ba7ad3-eac5-4938-90db-73b04551ea45/download
File
MD5
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application/pdf
Cohesin-SA1deficiencydrives_2012.pdf
URL
https://repisalud.isciii.es/bitstreams/b6822856-825d-40d0-acde-2fe1341fefaf/download
File
MD5
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text/plain
Cohesin-SA1deficiencydrives_2012.pdf.txt