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- Title
Co-localization of centromere activity, proteins and topoisomerase II within a subdomain of the major human X alpha-satellite array.
- Authors
Spence, Jennifer M; Critcher, Ricky; Ebersole, Thomas A; Valdivia, Manuel M; Earnshaw, William C; Fukagawa, Tatsuo; Farr, Christine J
- Abstract
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.
- Publication
The EMBO journal, 2002, Vol 21, Issue 19, p5269
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/cdf511