Journal of Molecular Biology
Volume 142, Issue 3, 25 September 1980, Pages 363-386
Journal home page for Journal of Molecular Biology

Sequence definition and organization of a human repeated DNA

https://doi.org/10.1016/0022-2836(80)90277-6Get rights and content

Abstract

DNA sequence data for a DNA repeated sequence, found largely in centromeres of specific human chromosomes is presented. The sequence consists of two tandem 169 and 171 base-pair units that show 27% base variation with each other. In contrast the dimer is more faithfully copied in longer tandem repeats, such as the sequenced 680 base-pair tetramer. In the major sequence of the tetramer, base variation of the order of only 1%, in comparison to the complete dimer is seen. A minimum of two steps in the formation of this sequence is proposed, consisting of evolution of a tandem dimer of two 170 base-pair variant units of a related family within the human genome, and later saltation or amplification of this dimer. No evidence that these sequences contained or evolved from a simpler 6 to 20 base-pair repeat was found, and no homology with known simpler human satellites could be discerned. In reviewing and comparing the literature on repeated DNAs it appears that overall length and tandem repetition are the critical features, rather than individual unit repeat length or secondary structural potential, in defining these sequences as a class and their special centromeric functions and higher chromosome order. The possibility that such sequences arise from a reservoir of interspersed sequences that are common to at least several species is discussed.

References (45)

  • P.A. Biro et al.

    J. Mol. Biol

    (1975)
  • P. Boseley et al.

    Cell

    (1979)
  • F.L. Brown et al.

    J. Mol. Biol

    (1979)
  • G. Corneo et al.

    Biochim. Biophys. Acta (Amst.)

    (1971)
  • L. Donehower et al.

    J. Mol. Biol

    (1979)
  • K. Fry et al.

    Cell

    (1977)
  • F. Galibert et al.

    J. Mol. Biol

    (1974)
  • J. Gosden et al.

    Exp. Cell Res

    (1975)
  • C.M. Houck et al.

    J. Mol. Biol

    (1979)
  • B. John et al.

    Int. Rev. Cytol

    (1979)
  • L. Manuelidis

    Anal. Biochem

    (1977)
  • P.R. Musich et al.

    J. Mol. Biol

    (1977)
  • C.M. Rubin et al.

    J. Mol. Biol

    (1980)
  • D.S. Singer

    J. Biol. Chem

    (1979)
  • R.S. Beauchamp et al.

    Chromosoma (Berl.)

    (1979)
  • S.D.M. Brown et al.

    Nucl. Acids Res

    (1979)
  • N. Christie et al.

    Nucl. Acids Res

    (1979)
  • H.J. Cooke

    Nucl. Acids Res

    (1979)
  • C. Duncan et al.
  • F. Fittler et al.

    Nucl. Acids Res

    (1979)
  • G.P. Holmquist et al.
  • W.R. Jelinek et al.
  • Cited by (180)

    • CENP-B-mediated DNA loops regulate activity and stability of human centromeres

      2022, Molecular Cell
      Citation Excerpt :

      Despite being epigenetically regulated, most centromeres across multiple species are enriched with particular types of AT-rich DNA sequences, raising questions on the functionality of such repeats (Dumont and Fachinetti, 2017; Talbert and Henikoff, 2020). In human cells, centromeres are built with a unique type of DNA tandem repeats, called α-satellites (α-sat) (Wu and Manuelidis, 1980), organized in a head-to-tail configuration of single AT-nucleotide-rich 171-bp monomers with high sequence similarity (Altemose et al., 2021). These monomers form larger repetitive units named higher order repeats (HORs) that span up to 5 Mb and represent ∼3% of the total genome (Logsdon et al., 2021; Miga et al., 2020).

    • Interaction of fluorescently labeled pyrrole-imidazole polyamide probes with fixed and living murine and human cells

      2018, Biochimie
      Citation Excerpt :

      It is present at both centromeres and pericentromeres. We have designed a 14 nucleotide probe (called PCY) for α-satellite DNA based on the conservation of the target sequence within numerous α-satellite DNA [23–25]. This probe labels large pericentromeric regions on almost all chromosomes, as revealed by FISH experiments (see further).

    • Genome-wide chromatin remodeling modulates the Alu heat shock response

      2001, Gene
      Citation Excerpt :

      This sequence is largely confined to centromeric regions (Wu and Manuelidis, 1980; van Holde, 1989). Because of this organization and the presence of sequence variants, digestion of alpha DNA with either Hae or Hinf alone primarily produces multiples of the fundamental 340 bp unit and some 171 bp monomers (Wu and Manuelidis, 1980). The Southern hybridization patterns observed for alpha satellite DNA should be distinguished from those observed for Alu.

    View all citing articles on Scopus

    This work was supported by a National Institutes of Health grant CA 15044 and a Research Career Development Award IKO4 NS 00101 (to L.M.).

    View full text