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Review
, 98 (15), 8173-80

Historical Overview: Searching for Replication Help in All of the Rec Places

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Review

Historical Overview: Searching for Replication Help in All of the Rec Places

M M Cox. Proc Natl Acad Sci U S A.

Abstract

For several decades, research into the mechanisms of genetic recombination proceeded without a complete understanding of its cellular function or its place in DNA metabolism. Many lines of research recently have coalesced to reveal a thorough integration of most aspects of DNA metabolism, including recombination. In bacteria, the primary function of homologous genetic recombination is the repair of stalled or collapsed replication forks. Recombinational DNA repair of replication forks is a surprisingly common process, even under normal growth conditions. The new results feature multiple pathways for repair and the involvement of many enzymatic systems. The long-recognized integration of replication and recombination in the DNA metabolism of bacteriophage T4 has moved into the spotlight with its clear mechanistic precedents. In eukaryotes, a similar integration of replication and recombination is seen in meiotic recombination as well as in the repair of replication forks and double-strand breaks generated by environmental abuse. Basic mechanisms for replication fork repair can now inform continued research into other aspects of recombination. This overview attempts to trace the history of the search for recombination function in bacteria and their bacteriophages, as well as some of the parallel paths taken in eukaryotic recombination research.

Figures

Figure 1
Figure 1
Pathways for recombinational DNA repair of a stalled replication fork. A pathway involving fork regression is shown for gap repair (af), and a double-strand break repair path is shown for the repair of a fork collapsed at the site of a DNA strand break (gl). The pathways shown are intended to be generic and do not incorporate all current ideas for fork repair. The dashed line represents a pathway in which the Holliday junction is converted to a double-strand break by the action of RuvABC, as observed by Michel and colleagues (180) and others. Arrowheads on DNA strands denote 3′ ends. If a DNA lesion (other than a strand break) is responsible for halting the progress of a replication fork, note that replication fork repair does not entail repair of the lesion itself. Instead, the recombination and replication steps set up the lesion for repair by providing an undamaged complementary DNA strand. The degree to which excision repair and other DNA repair processes are integrated with the recombinational repair pathways is unknown.
Figure 2
Figure 2
A replication intermediate from Drosophila embryos, photographed by Inman (49). One of the apparently regressed forks has a single-stranded tail (arrow). (Reprinted from Biochim. Biophys. Acta, 783, Inman, R. B., “Methodology for the study of the effect of drugs on development and DNA replication in Drosophila melanogaster embryonic tissue,” pp. 205–215, Copyright 1984, with permission from Excerpta Medica, Inc.; ref. .)

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