The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6 gene of Schizosaccharomyces pombe.

Grimm, Christian; Schaer, Pascal; Münz, Peter; Kohli, Jürg

doi:10.1128/mcb.11.1.289

Cited by 77 publications

(54 citation statements)

References 45 publications

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“…Eight crosses of 469 with M26 and four with M375 showed that the M26 hot spot had no detectable activity when the recombining ade6 genes were remote from their endogenous location ( Table 2, group C). [The 2-fold lower frequency with M26 than with M375 is within the range previously reported (2) (15). In our assays for M26 hot spot activity at ura4 the measured recombinant frequencies were lower than these values: 610 vs. 580 per 106 viable spores for M26 and M375, respectively, on the 0.35-kb insertions and 1900 vs. 3500 for M26 and M375, respectively, on the 3.0-kb insertions (Table 2, group B and group C).…”

Section: Resultssupporting

confidence: 72%

Chromosomal context dependence of a eukaryotic recombinational hot spot.

Ponticelli

Smith

1992

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

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The single base-pair mutation M26 in the ade6 gene of the fiion yeast Schizosaccharomyces pombe creates a hot spot for meiotic homologous recombination. When DNA fragments containing M26 and up to 3.0 kilobases of surrounding DNA were moved to the ura4 gene or to a multicopy plasmid, M26 had no detectable hot spot activity.Our results indicate that nucleotide sequences at least 1 kilobase away from M26 are required for M26 hot spot activity and suggest that, as for transcriptional promoters, a second site or proper chromatin structure is required for activation of this eukaryotic recombinational hot spot. We discuss the implications of these results for studies of other meiotic recombinational hot spots and for gene targeting.Special sites enhance homologous recombination within their vicinity on the chromosomes ofprokaryotes and eukaryotes (1). These sites, called hot spots, are thought to be recognition sites for recombination-promoting enzymes, which act at high frequency at or near the hot spot. Recombinational hot spots are thus analogous to promoters of transcription and origins of DNA replication, in that they define discrete chromosomal sites that stimulate chromosomal activity in their vicinity.The M26 mutation in the ade6 gene of Schizosaccharomyces pombe creates a recombinational hot spot (2) that enhances gene conversion and crossing-over at the ade6 locus but not at other loci; the M26 hot spot is active during meiosis but not during mitosis (3, 4). In some respects the M26 hot spot appears simple: it is a single base-pair change G-C -* T-A (3, 5) creating the sequence 5'-ATGACGT-3', which is required for hot spot activity (6). M26 acts when it is present on one or both of the recombining chromosomes (3). These results are consistent with the view that M26 is the recognition site for a sequence-specific recombination-promoting protein. Indeed, an M26-specific binding protein has recently been detected (E. Kaslin and J. Kohli, personal communication; W. Wahis and G.R.S., unpublished observations). We report here, however, that the requirements for M26 action are complex: when the M26 site with up to 3.0 kilobases (kb) of surrounding DNA was moved to other locations in the genome, it failed to enhance recombination. These results imply that the action of M26 requires another chromosomal site or proper surrounding chromatin structure. This complexity urges caution in the interpretation of large deletions that appear to locate other chromosomal sites, including recombinational hot spots.

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Section: Resultssupporting

confidence: 72%

Chromosomal context dependence of a eukaryotic recombinational hot spot.

Ponticelli

Smith

1992

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

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“…For the multiplicative function this was (1 Ϫ M ab ) 4 , the fraction of the population receiving no new mutations in each generation. This was identical to the viability of an asexual population and was not changed by recombination (compare lines 1, 2, and 3).…”

Section: Resultsmentioning

confidence: 99%

“…Most studies of the mechanism have been done in ascomycete fungi, where meiosis can be synchronously induced and all the meiotic products recovered in the ascus. Biased gene conversion is a typical consequence of recombination at hotspots (4)(5)(6). For example, a cross between active and inactive alleles of the ARG4 hotspot in the yeast Saccharomyces cerevisiae exhibits a 22-fold bias toward conversion of the active allele to its inactive homolog (6).…”

mentioning

confidence: 99%

The hotspot conversion paradox and the evolution of meiotic recombination

Boulton

Myers²,

Redfield

1997

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

177

199

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Studies of meiotic recombination have revealed an evolutionary paradox. Molecular and genetic analysis has shown that crossing over initiates at specific sites called hotspots, by a recombinational-repair mechanism in which the initiating hotspot is replaced by a copy of its homolog. We have used computer simulations of large populations to show that this mechanism causes active hotspot alleles to be rapidly replaced by inactive alleles, which arise by rare mutation and increase by recombination-associated conversion. Additional simulations solidified the paradox by showing that the known benefits of recombination appear inadequate to maintain its mechanism. Neither the benefits of accurate segregation nor those of recombining f lanking genes were sufficient to preserve active alleles in the face of conversion. A partial resolution to this paradox was obtained by introducing into the model an additional, nonmeiotic function for the sites that initiate recombination, consistent with the observed association of hotspots with functional sites in chromatin. Provided selection for this function was sufficiently strong, active hotspots were able to persist in spite of frequent conversion to inactive alleles. However, this explanation is unsatisfactory for two reasons. First, it is unlikely to apply to obligately sexual species, because observed crossover frequencies imply maintenance of many hotspots per genome, and the viability selection needed to preserve these would drive the species to extinction. Second, it fails to explain why such a genetically costly mechanism of recombination has been maintained over evolutionary time. Thus the paradox persists and is likely to be resolved only by significant changes to the commonly accepted mechanism of crossing over.Meiotic crossing over between homologous chromosomes plays two important roles in the genetic reshuffling caused by sexual reproduction: it creates new combinations of alleles within each chromosome, and it prevents nondisjunction during chromosome segregation (1). Crossovers are initiated primarily at specific sites called hotspots (2, 3). Most studies of the mechanism have been done in ascomycete fungi, where meiosis can be synchronously induced and all the meiotic products recovered in the ascus. Biased gene conversion is a typical consequence of recombination at hotspots (4-6). For example, a cross between active and inactive alleles of the ARG4 hotspot in the yeast Saccharomyces cerevisiae exhibits a 22-fold bias toward conversion of the active allele to its inactive homolog (6). Physical studies have shown that recombination events in S. cerevisiae are initiated by site-specific doublestrand DNA breaks at hotspots, before the visible pairing of the chromosomes (7, 8). As illustrated in Fig. 1, these breaks are thought to be repaired by DNA synthesis that uses the strands of the homologous chromosomes as templates, with resolution of the repair intermediate frequently creating a crossover between the participating chromosomes (9, 10). This and rela...

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“…One striking characteristic of hotspots is that they are subject to a form of meiotic drive: when a DSB occurs at a hotspot heterozygous for an active (''hot'') and an inactive (''cold'') hotspot allele, the cold allele tends to appear in a higher proportion of the offspring than does the hot allele (often in an $3:1 ratio rather than the expected 2:2) (Catcheside 1975;Nicolas et al 1989;Grimm et al 1991;Malone et al 1994;Guillon and De Massy 2002;Jeffreys and Neumann 2002;Jeffreys and May 2004;Cromie et al 2005). This is likely the result of the mechanism by which recombination is thought to be initiated: a doublestrand break (DSB) forms on one chromatid; this break extends a variable distance in the 59 direction on each strand; and the sequence of the nonsister chromatid is used as a template to repair the gap.…”

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confidence: 99%

A Combination of cis and trans Control Can Solve the Hotspot Conversion Paradox

Peters

2008

Genetics

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There is growing evidence that in a variety of organisms the majority of meiotic recombination events occur at a relatively small fraction of loci, known as recombination hotspots. If hotspot activity results from the DNA sequence at or near the hotspot itself (in cis), these hotspots are expected to be rapidly lost due to biased gene conversion, unless there is strong selection in favor of the hotspot itself. This phenomenon makes it very difficult to maintain existing hotspots and even more difficult for new hotspots to evolve; it has therefore come to be known as the ''hotspot conversion paradox.'' I develop an analytical framework for exploring the evolution of recombination hotspots under the forces of selection, mutation, and conversion. I derive the general conditions under which cis-and trans-controlled hotspots can be maintained, as well as those under which new hotspots controlled by both a cis and a trans locus can invade a population. I show that the conditions for maintenance of and invasion by trans-or cis-plus-trans-controlled hotspots are broader than for those controlled entirely in cis. Finally, I show that a combination of cis and trans control may allow for long-lived polymorphisms in hotspot activity, the patterns of which may explain some recently observed features of recombination hotspots.T HERE is growing evidence from several model systems across the eukaryotic phylogeny that meiotic recombination events, rather than being distributed uniformly across the genome, are largely concentrated into relatively small regions known as ''recombination hotspots.'' Hotspots in yeast (Malone et al.

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The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6 gene of Schizosaccharomyces pombe.

Cited by 77 publications

References 45 publications

Chromosomal context dependence of a eukaryotic recombinational hot spot.

Chromosomal context dependence of a eukaryotic recombinational hot spot.

The hotspot conversion paradox and the evolution of meiotic recombination

A Combination of cis and trans Control Can Solve the Hotspot Conversion Paradox

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