Co-localization of Centromere Activity, Proteins and Topoisomerase II Within a Subdomain of the Major Human X Alpha-satellite Array

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Oct 3

PMID 12356743

Citations 61

Authors

Jennifer M Spence

Ricky Critcher

Thomas A Ebersole

Manuel M Valdivia

William C Earnshaw

Tatsuo Fukagawa

Christine J Farr

Affiliations

Soon will be listed here.

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.

Citing Articles

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