Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis.
Drosophila MEI-S332 and fungal Sgo1 genes are essential for sister centromere cohesion in meiosis I. We demonstrate that the related vertebrate Sgo localizes to kinetochores and is required to prevent premature sister centromere separation in mitosis, thus providing an explanation for the differential cohesion observed between the arms and the centromeres of mitotic sister chromatids. Sgo is degraded by the anaphase-promoting complex, allowing the separation of sister centromeres in anaphase. Intriguingly, we show that Sgo interacts strongly with microtubules in vitro and that it regulates kinetochore microtubule stability in vivo, consistent with a direct microtubule interaction. Sgo is thus critical for mitotic progression and chromosome segregation and provides an unexpected link between sister centromere cohesion and microtubule interactions at kinetochores.
Salic
Adrian
A
Department of Systems Biology, 240 Longwood Avenue, Boston, MA 02115, USA. adrian_salic@hms.harvard.edu
Waters
Jennifer C
JC
Mitchison
Timothy J
TJ
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002478:Cells, Cultured; D002503:Centromere / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D018076:DNA, Complementary; D009687:Nuclear Proteins; C491611:Sgo protein, Xenopus; D029867:Xenopus Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome