Abstract
The centromere is an essential chromosomal structure that is required for the faithful distribution of replicated chromosomes to daughter cells. Defects in the centromere can compromise the stability of chromosomes resulting in segregation errors. We have characterised the centromeric structure of the spontaneous mutant mouse strain, BALB/cWt, which exhibits a high rate of Y chromosome instability. The Y centromere DNA array shows a de novo interstitial deletion and a reduction in the level of the foundation centromere protein, CENP-A, when compared to the non-deleted centromere array in the progenitor strain. These results suggest there is a lower threshold limit of centromere size that ensures full kinetochore function during cell division.
Highlights
The centromere is a multi-subunit DNA/protein structure that assembles a mature kinetochore after DNA replication in order to efficiently capture spindle microtubules for chromosome segregation
The functional centromere of the autosomes and the X chromosome is localised to the 120 bp minor satellite repeat DNA, which is organised in a head-to-tail arrangement spanning 300–600 kb [7,8]
Interstitial Deletion of the Y Centromere DNA Array Bean and colleagues have postulated that the Wt Y chromosome non disjunction was due to a ‘sub-optimal’ centromere [14]
Summary
The centromere is a multi-subunit DNA/protein structure that assembles a mature kinetochore after DNA replication in order to efficiently capture spindle microtubules for chromosome segregation. A subset of this repetitive DNA is functionally marked by centromere-specific nucleosomes containing the essential histone H3 variant, CENP-A plus other constitutive centromere proteins [3,4]. This chromatin is the foundation layer onto which mitotic-specific proteins assemble to form a mature kinetochore that modulates the timing and fidelity of chromosome attachment and movement during mitosis and meiosis [5,6]. The Y chromosome centromere is relatively small, containing only 90 kb of the diverged minor satellite repeat DNA known as Ymin [1]. The Y chromosome is an excellent model chromosome for studies into structural and functional centromere biology because it is haploid and has a diverged, small centromere
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