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Int. J. Mol. Sci. 2018, 19(2), 534; https://doi.org/10.3390/ijms19020534

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

1
Department of Genetics, University of Cambridge, Downing St, Cambridge CB2 3EH, UK
2
Laboratory of Chromosome Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Received: 12 January 2018 / Revised: 6 February 2018 / Accepted: 7 February 2018 / Published: 10 February 2018
(This article belongs to the Special Issue DNA Topoisomerases)
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Abstract

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. View Full-Text
Keywords: topoisomerase 2α (topo 2α); centromere; mitosis; etoposide; cleavage; secondary DNA structure topoisomerase 2α (topo 2α); centromere; mitosis; etoposide; cleavage; secondary DNA structure
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Mills, W.E.; Spence, J.M.; Fukagawa, T.; Farr, C.J. Site-Specific Cleavage by Topoisomerase 2: A Mark of the Core Centromere. Int. J. Mol. Sci. 2018, 19, 534.

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