Co-localization of centromere activity, proteins and topoisomerase II within a subdomain of the major human X alpha-satellite array.
Spence, Jennifer M;
Critcher, Ricky;
Ebersole, Thomas A;
Valdivia, Manuel M;
Earnshaw, William C;
Fukagawa, Tatsuo;
Farr, Christine J;
(2002)
Co-localization of centromere activity, proteins and topoisomerase II within a subdomain of the major human X alpha-satellite array.
The EMBO journal, 21 (19).
pp. 5269-5280.
ISSN 0261-4189
DOI: https://doi.org/10.1093/emboj/cdf511
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Dissection of human centromeres is difficult because of the lack of landmarks within highly repeated DNA. We have systematically manipulated a single human X centromere generating a large series of deletion derivatives, which have been examined at four levels: linear DNA structure; the distribution of constitutive centromere proteins; topoisomerase IIalpha cleavage activity; and mitotic stability. We have determined that the human X major alpha-satellite locus, DXZ1, is asymmetrically organized with an active subdomain anchored approximately 150 kb in from the Xp-edge. We demonstrate a major site of topoisomerase II cleavage within this domain that can shift if juxtaposed with a telomere, suggesting that this enzyme recognizes an epigenetic determinant within the DXZ1 chromatin. The observation that the only part of the DXZ1 locus shared by all deletion derivatives is a highly restricted region of <50 kb, which coincides with the topo isomerase II cleavage site, together with the high levels of cleavage detected, identify topoisomerase II as a major player in centromere biology.