Premium
Cohesin‐SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres
Author(s) -
Remeseiro Silvia,
Cuadrado Ana,
Carretero María,
Martínez Paula,
Drosopoulos William C,
Cañamero Marta,
Schildkraut Carl L,
Blasco María A,
Losada Ana
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.11
Subject(s) - telomerase , telomere , biology , cancer , library science , genetics , gene , computer science
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.