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Topoisomerase II cleavage activity within the human D11Z1 and DXZ1 alpha-satellite arrays

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Abstract

Topoisomerase II (Topo II) is a major component of mitotic chromosomes and its unique decatenating activity has been implicated in many aspects of chromosome dynamics including DNA replication, transcription, recombination, chromosome condensation and segregation. Of these, chromosome segregation is the most seriously affected by loss of Topo II, most probably because of residual catenations between sister chromatids. At metaphase, vertebrate chromatids are attached principally through their centromeric regions. Intriguingly, evidence has recently been presented for Topo II cleavage activity within the centromeric α-satellite DNA arrays of the human X and Y chromosomes. In this report we extend these observations by mapping distinct sites of Topo II cleavage activity within the α-satellite array of human chromosome 11. A single major site of cleavage has been assigned within the centromeric DNA of each of three independently derived, and active, 11 centromeres. Unlike the X and Y centromeres, where cleavage sites mapped close to (within 150 kb of) the short arm edge of the arrays, on chromosome 11, the cleavage sites lie many hundreds of kilobases into each α-satellite array. We also demonstrate that catalytically active Topo II is concentrated within the centromere domain through an extended period of G2 and M, with levels declining in G1 and S.

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Authors and Affiliations

  1. Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK

    Jennifer M. Spence & Christine J. Farr

  2. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    R. E. Keith Fournier

  3. Graduate School of Medical Sciences, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan

    Mitsuo Oshimura

  4. Universite Paris 7—Denis Diderot, Campus Jussieu, Case 7104, 2 Place Jussieu, 75251, Paris Cedex 05, France

    Vinciane Regnier

Authors
  1. Jennifer M. Spence
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  2. R. E. Keith Fournier
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  3. Mitsuo Oshimura
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  4. Vinciane Regnier
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  5. Christine J. Farr
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Correspondence to Christine J. Farr.

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Spence, J.M., Fournier, R.E.K., Oshimura, M. et al. Topoisomerase II cleavage activity within the human D11Z1 and DXZ1 alpha-satellite arrays. Chromosome Res 13, 637–648 (2005). https://doi.org/10.1007/s10577-005-1003-8

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  • DOI: https://doi.org/10.1007/s10577-005-1003-8

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