Site-specific Initiation of DNA Replication in Metazoan Chromosomes and the Role of Nuclear Organization

  1. D.M. Gilbert*,
  2. H. Miyazawa*,
  3. F.S. Nallaseth*,
  4. J.M. Ortega*,
  5. J.J. Blow, and
  6. M.L. DePamphilis*
  1. *Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110; ICRF Clare Hall Laboratories, South Mimms, Potters Bar, Herts EN63LD, United Kingdom

This extract was created in the absence of an abstract.

Excerpt

Analyses of DNA replication in “simple” genomes that replicate in eukaryotic cells such as animal viruses and mitochondria as well as the chromosomes in protozoa (Tetrahymena), yeast (Saccharomyces), and slime mold (Physarum) have led to the generally held view that replication begins when specific proteins bind specific DNA sequences to initiate DNA unwinding at or near the binding site (for review, see Kornberg and Baker 1992; DePamphilis 1993a). This event is followed rapidly by initiation of DNA synthesis on one or both DNA templates. DNA replication in cellular chromosomes of differentiated cells as well as in circular DNA molecules that replicate in their nuclei, such as papovaviruses and papillomaviruses, all utilize the standard replication fork mechanism outlined in Figure 1 (for review, see Burhans et al. 1990). DNA is synthesized continuously on the forward arm (leading strand) but discontinuously on the retrograde arm (lagging strand) by the repeated synthesis and...

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