Premium
Co‐localization of centromere activity, proteins and topoisomerase II within a subdomain of the major human X α‐satellite array
Author(s) -
Spence Jennifer M.,
Critcher Ricky,
Ebersole Thomas A.,
Valdivia Manuel M.,
Earnshaw William C.,
Fukagawa Tatsuo,
Farr Christine J.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf511
Subject(s) - biology , centromere , topoisomerase , satellite , computational biology , genetics , satellite dna , dna , microbiology and biotechnology , gene , chromosome , engineering , aerospace engineering
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 IIα cleavage activity; and mitotic stability. We have determined that the human X major α‐satellite locus, DXZ1, is asymmetrically organized with an active subdomain anchored ∼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.