A general model for genetic recombination.

Abstract

A general model is proposed for genetic recombination. Its essential new feature is the hypothesis that recombination is initiated by a single-strand (or asymmetric) transfer, which may, after isomerization, become a two-strand (or symmetric) exchange. The likelihood of this transition from asymmetric to symmetric strand exchange determines certain characteristic features of recombination in any particular organism.In eukaryotes the segregation of an allele pair among the four products of meiosis occasionally departs from the usual 2:2 ratio while the segregation of well-separated markers on either side remains normal (i.e., 2:2). Frequently the flanking markers are recombined. This pattern, derived largely from genetic studies in fungi, probably means that the region of aberrant segregation is the actual site of chemical interaction between two recombining DNA molecules. Genetic analysis in fungi and prokaryotes, considerations of DNA structure, and the recognition of a number of enzymic mechanisms of DNA chemistry have made it possible to formulate rather specific hypotheses about molecular aspects of recombination, as we do in this paper (see refs. 1 and 2 for reviews). The Holliday modelIn 1964 Holliday proposed a model to explain recombination and aberrant segregation in fungi (3). Two homologous DNA duplexes, each corresponding to one of the four chromatids present at meiosis, undergo single-strand breakage and exchange single strands, forming heteroduplex DNA symmetrically for a limited distance as depicted in Fig. 1 (p,p in Fig. 1) leaves the flanking arms in the parental configuration, whereas cleavage of the other pair of strands (r,r) yields products with the flanking arms in the recombinant configuration.Recently, Sigal and Alberts (4) constructed a molecular model of the Holliday structure and found that it can be built with satisfactory bond lengths and angles, with no bases unpaired. The cross connection can move up or down by rotation of both duplexes in the same sense, a process that could be driven by rotary diffusion (5). Migration of the cross connection extends the region of heteroduplex DNA symmetrically on both chromatids, giving the postulated recombination intermediate (Fig. 1). Heteroduplex DNA in one versus two chromatidsThe equal formation of heteroduplex DNA on both chromatids, which is an intrinsic feature of the Holliday structure, should be reflected in the genetic data. The relevant evidence is mixed. The occurrence of aberrant 4:4 segregations in Sordaria indicates that heteroduplex DNA can form at the same site on both chromatids (6). At the b2 locus in Ascobolus, Leblon and Rossignol (7) observed that the ratios of 6:2, 5:3, and aberrant 4:4 segregations were in good agreement with the hypothesis that heteroduplex DNA usually forms on both chromatids. In contrast, other studies are most simply interpreted to mean that heteroduplex DNA usually forms on only one chromatid. At the arg4 locus in yeast the frequency of intragenic two-strand (i.e., two-chromatid) double e...

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“…4, which is based on the model of M Meselson & Radding (1975). The transfer of a parental strand from one daughter molecule to the other leads to the formation of hybrid DNA containing methyl groups on both strands, and damage in one.…”

Repairing a double–strand chromosome break by homologous recombination: revisiting Robin Holliday's model

“…A similar, but more elaborated model, presented by Szostak, Orr-Weaver, Rothstein and Stahl (1983), gained wide acceptance a few years later. This DSB repair model (figure 2a) was based primarily on studies of transformation and gene targeting in budding yeast Rothstein 1983), but it provided explanations for many observations that had not been accounted for by the model of Holliday (1964) or by its successor, the single-strand nick model of Meselson & Radding (1975). In this model, recombination is initiated by ssDNA that was created by 5Ј to 3Ј exonucleases resecting the ends of the DSB.…”

Recombination in diploid vegetative cells of Saccharomyces cerevisiae

“…The failure to obtain certain types of aberrant segregation in proportions expected from a simple interpretation of the HOLLIDAY proposal cast doubt on the twin heteroduplex hypothesis, and suggested instead that a single heteroduplex in only one of the two homologs was not uncommon. MESEL-SON and RADDING (9) proposed a unifying hypothesis that involves single strand transfer from one homolog to the other as a result of strand displacement to form a single region of hybrid DNA. By strand isomerization (15), and branch migration, the asymmetric phase, in which one chromatid has the single heteroduplex, becomes symmetric, with hybrid DNA in 0105-1938/80/0045/0211/$ 02.80 both chromatids.…”