Evidence on the chromosomal location of centromeric DNA in Plasmodium falciparum from etoposide-mediated topoisomerase-II cleavage.
Kelly, John M;
McRobert, Louisa;
Baker, David A;
(2006)
Evidence on the chromosomal location of centromeric DNA in Plasmodium falciparum from etoposide-mediated topoisomerase-II cleavage.
Proceedings of the National Academy of Sciences of the United States of America, 103 (17).
pp. 6706-6711.
ISSN 0027-8424
DOI: https://doi.org/10.1073/pnas.0510363103
Permanent Identifier
Use this Digital Object Identifier when citing or linking to this resource.
Centromeres are the chromosomal loci that facilitate segregation, and, in most eukaryotes, they encompass extensive regions of genomic DNA. Topoisomerase-II has been identified as a crucial regulator of segregation in a wide range of organisms and exhibits premitotic accumulation at centromeres. Consistent with this property, treatment of cells with the topoisomerase-II inhibitor etoposide promotes chromosomal cleavage at sites within centromeric DNA. In the case of the human malaria parasite Plasmodium falciparum, despite a completed genome sequence, there are no experimental data on the nature of centromeres. To address this issue, we have used etoposide-mediated topoisomerase-II cleavage as a biochemical marker to map centromeric DNA on all 14 parasite chromosomes. We find that topoisomerase-II activity is concentrated at single chromosomal loci and that cleavage sites extend over approximately 10 kb. A shared feature of these topoisomerase-II cleavage sites is the presence of an extremely AT-rich ( approximately 97%) domain with a strictly defined size limit of 2.3-2.5 kb. Repetitive arrays identified within the domains do not display interchromosomal conservation in terms of length, copy number, or sequence. These unusual properties suggest that P. falciparum chromosomes contain a class of "regional" centromere distinct from those described in other eukaryotes, including the human host.