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Abstract
Analysis of centromeric DNA and kinetochore proteins suggests that critical structural features of kinetochores have been well conserved from yeast to man.
Highlights
Kinetochores are large multi-protein structures that assemble on centromeric DNA (CEN DNA) and mediate the binding of chromosomes to microtubules
CDEII is not conserved in sequence but, rather, is characterized by high AT content and alternating runs of poly-A and poly-T. To capture this information we constructed a tri-partite computational model based on profiles for CDEI and CDEIII, a hidden Markov model (HMM) for CDEII (Figure 1a), and S. cerevisiae CENs as a training set
When the model was tested on C. glabrata, E. gossypii and K. lactis, organisms whose genomes are fully annotated, 6/13 centromeres in C. glabrata, 6/7 centromeres in E. gossypii and 6/6 in K. lactis were identified correctly (Figure 1b)
Summary
Kinetochores are large multi-protein structures that assemble on centromeric DNA (CEN DNA) and mediate the binding of chromosomes to microtubules. The simplest known CENs, those in the budding yeast Saccharomyces cerevisiae, consist of 125 base-pairs (bp) of DNA and three protein-binding motifs (CDEI, CDEII and CDEIII) that are present on all 16 chromosomes [4] These short CEN sequences, often called 'point' CENs, are structurally similar to enhancers and transcriptional regulators in that their assembly is initiated by highly sequence-selective DNA-protein interactions [5]. CEN DNA in fungi such as the budding yeast Candida albicans and fission yeast Schizosaccharomyces pombe, plants such as Arabidopsis thaliana, and metazoans such as Drosophila melanogaster and Homo sapiens, are longer and more complex and exhibit poor sequence conservation [610] These regional CENs range in size from 1 kb in C. albicans [6], to several megabases in H. sapiens [8] and typically contain long stretches of repetitive AT-rich DNA. Sequence-selective DNA-protein interactions have not been identified in regional CENs and it is thought that kinetochore position is determined by a specialized chromatin domain whose formation at one site on each chromosome is controlled by epigenetic mechanisms [2,12]
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