Differential subcellular localizations of two human Sgo1 isoforms: implications in regulation of sister chromatid cohesion and microtubule dynamics.
Sgo1 is an evolutionarily conserved protein that functions as a protector of centromeric cohesin during mitosis. Recent studies show that Sgo1 is kinetochorelocalized and required for accurate segregation of mitotic chromosomes because depletion of Sgo1 in mammalian cells results in precocious initiation of anaphase and mis-segregation of chromosomes. Through analysis of GFP fusion proteins, we observe that two major isoforms of human Sgo1 exhibit entirely different subcellular localization patterns. The short isoform of Sgo1 (sSgo1) that lacks exon 6 does not localize to kinetochores during any stages of the cell cycle. Instead, it is enriched at mitotic spindles. On the other hand, the longer isoform of Sgo1 primarily localizes to kinetochores during G(2) phase and mitotic prophase, metaphase, and anaphase. During late mitosis, Sgo1 does not appear to be associated with kinetochores. Intriguingly, the longer isoform of Sgo1 forms discrete foci during S phase, some of which are apparently in the nucleoli. However, a majority of these foci colocalize with CREST, a kinetochore antigen, indicating that Sgo1 is loaded onto kinetochores during or immediately after DNA replication. Together, our studies suggest that different isoforms of Sgo1 may play distinct roles during the cell cycle and that Sgo1 may have an interphase function as well.
Division of Molecular Carcinogenesis, Department of Medicine, New York Medical College, Valhalla, New York, USA.
Xiaoxing
X
Wang
Yali
Y
Yang
Wei
W
Dai
D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002842:Chromatids / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics
D018797:Cell Cycle Proteins; D020033:Protein Isoforms; C496644:SGO1 protein, human; C502810:SS18L1 protein, human; D015534:Trans-Activators