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Chromatin Structure, DNA Sequences and Replication Proteins: Searching for the Principles of Eukaryotic Chromosome Replication

  • Melvin L. DePamphilis
  • Michael E. Cusick
  • Ronald T. Hay
  • Cynthia Pritchard
  • Lois C. Tack
  • Paul M. Wassarman
  • David T. Weaver

Abstract

Our objective has been to understand, at the molecular level, the replication of eukaryotic chromosomes as a prerequisite to investigating the regulation of chromosome replication and its relationship to cell proliferation. Chromosomes from eukaryotic cells, simian virus 40 and polyoma virus consist of a series of nucleosomes, each containing about 200bp of DNA coiled around an octamer consisting of two each of the four core histones that gives chromatin its stable repeating structure. Additional structure is provided by histone H1 and non-histone chromosomal proteins. However, chromatin is not homogenous. The chromatin structure of quiescent genes differs from that of active genes, and chromosomal regions differ in their higher-ordered structure. For example, chromatin can be euchromatic or heterochromatic, 10nm thick fibers or 30nm thick coils, folded into loops or not folded. Therefore, replication of eukaryotic chromosomes, in contrast to prokaryotic chromosomes, requires accurate duplication of the structure of both chromatin and DNA. Furthermore, both chromatin structure and DNA sequence are likely involved in controlling replication by modifying the interaction of proteins with DNA. For example, nonuniformly spaced clusters of replication origins are activated at different times during S phase, but the same origin is never activated twice, and some origins that are active in embryonic cells are not used in somatic cells9. Once a replicon is activated, replication proteins must be directed to replication forks and termination of replication must result in complete separation of sibling chromatids to allow normal mitosis.

Keywords

Replication Fork Replicate Intermediate Okazaki Fragment MNase Digestion SV40 Genome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Melvin L. DePamphilis
    • 1
  • Michael E. Cusick
    • 1
  • Ronald T. Hay
    • 1
  • Cynthia Pritchard
    • 1
  • Lois C. Tack
    • 1
  • Paul M. Wassarman
    • 1
  • David T. Weaver
    • 1
  1. 1.Department of Biological ChemistryHarvard Medical SchoolBostonUSA

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