title: Shugoshin-2 is essential for the completion of meiosis but not for mitotic cell division in mice.
abstract: Shugoshin-2 (SGOL2) is one of the two mammalian orthologs of the Shugoshin/Mei-S322 family of proteins that regulate sister chromatid cohesion by protecting the integrity of the multiprotein cohesin complexes. This protective system is essential for faithful chromosome segregation during mitosis and meiosis, which is the physical basis of Mendelian inheritance. Regardless of its evolutionary conservation from yeast to mammals, little is known about the in vivo relevance and specific role that SGOL2 plays in mammals. Here we show that disruption of the gene encoding mouse SGOL2 does not cause any alteration in sister chromatid cohesion in embryonic cultured fibroblasts and adult somatic tissues. Moreover, mutant mice develop normally and survive to adulthood without any apparent alteration. However, both male and female Sgol2-deficient mice are infertile. We demonstrate that SGOL2 is necessary for protecting centromeric cohesion during mammalian meiosis I. In vivo, the loss of SGOL2 promotes a premature release of the meiosis-specific REC8 cohesin complexes from anaphase I centromeres. This molecular alteration is manifested cytologically by the complete loss of centromere cohesion at metaphase II leading to single chromatids and physiologically with the formation of aneuploid gametes that give rise to infertility.
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer (CSIC-USAL), Campus Miguel de Unamuno, 37007 Salamanca, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Llano
authors.forename: Rocío
authors.initials: R
authors.lastname: Gómez
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez-Caballero
authors.forename: Yurema
authors.initials: Y
authors.lastname: Herrán
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Martín
authors.forename: Luis
authors.initials: L
authors.lastname: Vázquez-Quiñones
authors.forename: Teresa
authors.initials: T
authors.lastname: Hernández
authors.forename: Enrique
authors.initials: E
authors.lastname: de Alava
authors.forename: Ana
authors.initials: A
authors.lastname: Cuadrado
authors.forename: José Luis
authors.initials: JL
authors.lastname: Barbero
authors.forename: José A
authors.initials: JA
authors.lastname: Suja
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pendás