Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles

Abstract

We show that female sterile mutations of aurora (aur) are allelic to mutations in the lethal complementation group ck10. This lies in a cytogenetic interval, 87A7-A9, that contains eight transcription units. A 250 bp region upstream of both aur and a divergent transcription unit corresponds to the site of a specific chromatin structure (scs') previously proposed to be a barrier to insulate enhancers of the major hsp70 gene at 87A7. Syncytial embryos derived from aur mothers display closely paired centrosomes at inappropriate mitotic stages and develop interconnected spindles in which the poles are shared. Amorphic alleles result in pupal lethality and in mitotic arrest in which condensed chromosomes are arranged on circular monopolar spindles. The size of the single centrosomal body in these circular figures suggests that loss of function of the serine-threonine protein kinase encoded by aur leads to a failure of the centrosomes to separate and form a bipolar spindle.

A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines

“…Temperature sensitive conditional S cerevisae IplI mutants missegregate chromosomes at restrictive temperature (Chan and Botstein, 1993). Mutations in the gene aurora in Drosophila have been reported to give rise to chromosome segregation abnormalities ranging from generation of polyploid nuclei to mitotic arrest depending on the allelic variants of the locus involved (Glover et al, 1995). Signi®cant sequence homology shared by Ipl1, aurora and BTAK suggests that these proteins belong to a family of conserved protein serine/threonine kinases which are involved in regulation of chromosome segregation process.…”

“…In this paper we describe isolation, by direct selection, of a partial cDNA sequence for a putative serine/threnonine kinase encoding gene harbored on chromosome 20q13 that is ampli®ed and overexpressed in human breast cancer cell lines. This novel gene being called BTAK (Breast Tumor Ampli®ed Kinase) shares signi®cant homology with the kinase domains of yeast and Drosophila kinase known to be involved in chromosome segregation (Francisco et al, 1994;Glover et al, 1995). BTAK gene maps close to the region on 20q amplicon that has been associated with aggressive breast cancer.…”

Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway

“…The yeast IPL1 and Drosophila aurora are required for chromosome segregation and centrosome maturation and constitute a family of serine/threonine kinases (Francisco et al, 1994;Glover et al, 1995). The IPL1 gene was identi®ed originally in a screen for yeast mutants that increase in ploidy (Francisco et al, 1994).…”

Function and regulation of Aurora/Ipl1p kinase family in cell division

“…The founding members of the Aurora kinase family are IpI1p from budding yeast S. cerevisiae, based on a pioneering genetic screen for mutations that lead to increase in chromosome mis-segregation [3], and Aurora from Drosophila melanogaster [4]. While IpI1p is the only Aurora kinase in yeast, there are two Aurora kinases in Drosophila melanogaster, and C. elegans [5,6], and at least three members in human [7].…”

“…Furthermore, Aurora-A is required for the accumulation of centrosomal gtubulin and other two PCM components as embryo enters mitosis. In Drosophila, mutations in Aurora lead to unseparated centrosome and monopolar spindle [4]. In Xenopus, Eg2 (the homolog of Aurora-A) situates around PCM during interphase, but relocates on spindle microtubule in anaphase [12].…”