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Published 26 November 2001. doi:10.1083/jcb.200105029
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© The Rockefeller University Press, 0021-9525/2001/11/763 $5.00
The Journal of Cell Biology, Volume 155, Number 5, November 26, 2001 763-774

Article

Functional cooperation of Dam1, Ipl1, and the inner centromere protein (INCENP)–related protein Sli15 during chromosome segregation



Jung-seog Kang1, Iain M. Cheeseman2, George Kallstrom1, Soundarapandian Velmurugan1, Georjana Barnes2 and Clarence S.M. Chan1

1 Section of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, The University of Texas, Austin, TX 78712
2 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

Address correspondence to Clarence S.M. Chan, Section of Molecular Genetics and Microbiology, ESB 226, The University of Texas at Austin, Austin, TX 78712. Tel.: (512) 471-6860. Fax: (512) 471-7088. E-mail: clarence_chan{at}mail.utexas.edu

We have shown previously that Ipl1 and Sli15 are required for chromosome segregation in Saccharomyces cerevisiae. Sli15 associates directly with the Ipl1 protein kinase and these two proteins colocalize to the mitotic spindle. We show here that Sli15 stimulates the in vitro, and likely in vivo, kinase activity of Ipl1, and Sli15 facilitates the association of Ipl1 with the mitotic spindle. The Ipl1-binding and -stimulating activities of Sli15 both reside within a region containing homology to the metazoan inner centromere protein (INCENP). Ipl1 and Sli15 also bind to Dam1, a microtubule-binding protein required for mitotic spindle integrity and kinetochore function. Sli15 and Dam1 are most likely physiological targets of Ipl1 since Ipl1 can phosphorylate both proteins efficiently in vitro, and the in vivo phosphorylation of both proteins is reduced in ipl1 mutants. Some dam1 mutations exacerbate the phenotype of ipl1 and sli15 mutants, thus providing evidence that Dam1 interactions with Ipl1–Sli15 are functionally important in vivo. Similar to Dam1, Ipl1 and Sli15 each bind to microtubules directly in vitro, and they are associated with yeast centromeric DNA in vivo. Given their dual association with microtubules and kinetochores, Ipl1, Sli15, and Dam1 may play crucial roles in regulating chromosome–spindle interactions or in the movement of kinetochores along microtubules.

Key Words: chromosome segregation; Ipl1; Sli15; Dam1; kinetochore


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