Site-Specific Cleavage by Topoisomerase 2: A Mark of the Core Centromere.

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Mills, Walter E 
Spence, Jennifer M 
Fukagawa, Tatsuo 
Farr, Christine J 

In addition to its roles in transcription and replication, topoisomerase 2 (topo 2) is crucial in shaping mitotic chromosomes and in ensuring the orderly separation of sister chromatids. As well as its recruitment throughout the length of the mitotic chromosome, topo 2 accumulates at the primary constriction. Here, following cohesin release, the enzymatic activity of topo 2 acts to remove residual sister catenations. Intriguingly, topo 2 does not bind and cleave all sites in the genome equally; one preferred site of cleavage is within the core centromere. Discrete topo 2-centromeric cleavage sites have been identified in α-satellite DNA arrays of active human centromeres and in the centromere regions of some protozoans. In this study, we show that topo 2 cleavage sites are also a feature of the centromere in Schizosaccharomyces pombe, the metazoan Drosophila melanogaster and in another vertebrate species, Gallus gallus (chicken). In vertebrates, we show that this site-specific cleavage is diminished by depletion of CENP-I, an essential constitutive centromere protein. The presence, within the core centromere of a wide range of eukaryotes, of precise sites hypersensitive to topo 2 cleavage suggests that these mark a fundamental and conserved aspect of this functional domain, such as a non-canonical secondary structure.

centromere, cleavage, etoposide, mitosis, secondary DNA structure, topoisomerase 2α (topo 2α), Animals, Cell Cycle Proteins, Cell Line, Centromere, Centromere Protein A, Chickens, Chromosomal Proteins, Non-Histone, DNA Topoisomerases, Type II, DNA, Satellite, Drosophila melanogaster, Humans, Schizosaccharomyces
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Int J Mol Sci
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Cancer Research UK (C9609/A3527)
BBSRC (BBS/B/04994)