Next Article in Journal
Potential Antitumor Activity of 2-O-α-d-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-l-Ascorbic Acid
Previous Article in Journal
High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
Previous Article in Special Issue
Novel Bacterial Topoisomerase Inhibitors Exploit Asp83 and the Intrinsic Flexibility of the DNA Gyrase Binding Site
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(2), 534; doi: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)
View Full-Text   |   Download PDF [12860 KB, uploaded 10 February 2018]   |  

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top