Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 19, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/ijms19020534
Keywords
topoisomerase 2 (topo 2); centromere; mitosis; etoposide; cleavage; secondary DNA structure
Funding
- Cancer Research-UK [C9609/A3527]
- Biotechnology and Biological Sciences Research Council [BBS/B/04994]
- University of Cambridge RCUK block fund
- Biotechnology and Biological Sciences Research Council [BBS/B/04994] Funding Source: researchfish
Ask authors/readers for more resources
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 -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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available