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PMID:18765791

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Citation

Llano, E, Gómez, R, Gutiérrez-Caballero, C, Herrán, Y, Sánchez-Martín, M, Vázquez-Quiñones, L, Hernández, T, de Alava, E, Cuadrado, A, Barbero, JL, Suja, JA and Pendás, AM (2008) Shugoshin-2 is essential for the completion of meiosis but not for mitotic cell division in mice. Genes Dev. 22:2400-13

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.

Links

PubMed PMC2532928 Online version:10.1101/gad.475308

Keywords

Anaphase/physiology; Aneuploidy; Animals; Base Sequence; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cell Cycle Proteins/physiology; Cells, Cultured; Centromere/physiology; Chromosomal Proteins, Non-Histone/metabolism; Female; Fibroblasts/cytology; Fibroblasts/metabolism; Infertility, Female/genetics; Infertility, Female/metabolism; Infertility, Male/genetics; Infertility, Male/metabolism; Male; Meiosis/physiology; Mice; Mice, Knockout; Mitosis/physiology; Molecular Sequence Data; Nuclear Proteins/metabolism; Phosphoproteins/metabolism; Promoter Regions, Genetic; Sister Chromatid Exchange; Spermatocytes/metabolism; Spermatocytes/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CENPE

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:SGO2

located_in

GO:0000779: condensed chromosome, centromeric region

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)|part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:SGO2

acts_upstream_of_or_within

GO:0007143: female meiotic nuclear division

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3809644

P

Seeded From UniProt

complete

MOUSE:SGO2

acts_upstream_of_or_within

GO:0007140: male meiotic nuclear division

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3809644

P

Seeded From UniProt

complete

MOUSE:SGO2

acts_upstream_of_or_within

GO:2000711: positive regulation of maintenance of meiotic sister chromatid cohesion, centromeric

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3809644

P

  • regulates_o_occurs_in:(CL:0000017)|regulates_o_occurs_in:(CL:0000023)

Seeded From UniProt

complete

MOUSE:REC8

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:BUB1B

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete


See also

References

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