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Originally published as MBC in Press, 10.1091/mbc.E08-10-1011 on January 21, 2009

Vol. 20, Issue 6, 1772-1784, March 15, 2009

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Nbl1p: A Borealin/Dasra/CSC-1-like Protein Essential for Aurora/Ipl1 Complex Function and Integrity in Saccharomyces cerevisiae

Yuko Nakajima*, Randall G. Tyers*, Catherine C.L. Wong{dagger}, John R. Yates, III{dagger}, David G. Drubin*, and Georjana Barnes*

*Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720; and {dagger}Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037

Submitted October 10, 2008; Revised January 8, 2009; Accepted January 13, 2009
Monitoring Editor: Kerry S. Bloom

The Aurora kinase complex, also called the chromosomal passenger complex (CPC), is essential for faithful chromosome segregation and completion of cell division. In Fungi and Animalia, this complex consists of the kinase Aurora B/AIR-2/Ipl1p, INCENP/ICP-1/Sli15p, and Survivin/BIR-1/Bir1p. A fourth subunit, Borealin/Dasra/CSC-1, is required for CPC targeting to centromeres and central spindles and has only been found in Animalia. Here we identified a new core component of the CPC in budding yeast, Nbl1p. NBL1 is essential for viability and nbl1 mutations cause chromosome missegregation and lagging chromosomes. Nbl1p colocalizes and copurifies with the CPC, and it is essential for CPC localization, stability, integrity, and function. Nbl1p is related to the N-terminus of Borealin/Dasra/CSC-1 and is similarly involved in connecting the other CPC subunits. Distant homology searching identified nearly 200, mostly unannotated, Borealin/Dasra/CSC-1–related proteins from nearly 150 species within Fungi and Animalia. Analysis of the sequence of these proteins, combined with comparative protein structure modeling of Bir1p-Nbl1p-Sli15p using the crystal structure of the human Survivin–Borealin–INCENP complex, revealed a striking structural conservation across a broad range of species. Our biological and computational analyses therefore establish that the fundamental design of the CPC is conserved from Fungi to Animalia.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-10-1011) on January 21, 2009.

Address correspondence to: Georjana Barnes (gbarnes{at}berkeley.edu)

Abbreviations used: CPC, chromosomal passenger complex, aka Aurora/Ipl1 complex; MT, microtubule; THB, three-helix bundle of the CPC; HMM, Hidden Markov Model.




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