absolutely unfailing way. This problem is largely ignored in traditional studies on eukaryotic DNA replication.
Summary
A hypothesis for the control of eukaryotic DNA replication at the chromosomal level is proposed. The specific regulatory problem arises from the subdivision of the genome into thousands of individually replicating units, each of which must be duplicated a single time during S-phase. The hypothesis is based on the finding of direct repeats at replication origins. Such repeats can adopt, beyond the full-length double helical structure, another configuration exposing two single-stranded loops that provide suitable templates for the initiation of DNA replication. Any further initiation at the same origin is excluded as the single strandedness is eliminated by the replication process. Restoration of the initiable loop structure is proposed to occur by DNAprotein rearrangements involved in chromosome condensation and duplication of the chromosomal protein backbone during mitosis. A possible role of the maturation promoting factor (MPF) is suggested.
The Problem
Duplication of cellular and viral genomes starts with the onset of DNA synthesis at specific replication origins. Studies on the regulation of replication in general deal with the initiation process and the factors involved in it. All evidence gathered to date suggests that DNA replication, once initiated, proceeds without interruption until the entire genome is duplicated. In prokaryotes, no further regulatory device appears to be required for the replication of their genomes.
Regulation of DNA replication in eukaryotic cells is more complicated owing to the subdivision of the genome into a great number of replication units('.'). Each of the thousands of replicons, or groups of them. can be reproduced independently from each other at different times of the S phase. Obviously, some specific control mechanism must effectively prevent the reinitiation of replicons that have already been replicated earlier in the same S phase. An uncontrolled reinitiation would result in a genetically intolerable imbalance of genes. In view of the many replication origins that have to be initiated in the course of every Sphase. it has to be emphasized that any mechanism responsible for the control must operate in an