DNA motif associated with meiotic double‐strand break regions in <i>Saccharomyces cerevisiae</i>

Blumental‐Perry, Anna; Zenvirth, Drora; Klein, Shoshana; Onn, Itay; Simchen, Giora

doi:10.1093/embo-reports/kvd047

Cited by 21 publications

(29 citation statements)

References 25 publications

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“…None were found. Blumenthal-Perry et al (29) reported a motif associated with some recombination hotspots. We found no striking correlation between this motif and the hotspots identified in our study, suggesting that this motif might be associated with a subset of hotspots.…”

Section: Relationship Between Hotspots and Known Repetitive Chromosomalmentioning

confidence: 99%

Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae

Gerton

DeRisi²,

Shroff³

et al. 2000

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

464

517

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In the yeast Saccharomyces cerevisiae, meiotic recombination is initiated by double-strand DNA breaks (DSBs). Meiotic DSBs occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). We used DNA microarrays to estimate variation in the level of nearby meiotic DSBs for all 6,200 yeast genes. Hotspots were nonrandomly associated with regions of high G ؉ C base composition and certain transcriptional profiles. Coldspots were nonrandomly associated with the centromeres and telomeres. Hotspots are genomic regions with unusually high levels of recombination (1). From studies in yeast, several generalizations concerning hotspots can be made. First, most hotspots are intergenic rather than intragenic (2). Second, genetically defined hotspots are associated with local double-strand DNA breaks (DSBs) (1). Third, DSBs usually occur in DNase Isensitive regions (3). Fourth, activity of the HIS4 hotspot in Saccharomyces cerevisiae requires the binding of transcription factors in the hotspot region (4-6), but does not require high levels of meiosis-specific transcription (7). Hotspots that require transcription factor binding are called ␣ hotspots (8). Fifth, certain DNA sequences result in hotspots (␤ hotspots) that do not require the binding of known transcription factors (9).Meiotic DSB formation requires Spo11p, a topoisomerase II-related protein that is transiently covalently attached to the 5Ј ends of the DNA fragments (10, 11). In wild-type yeast cells, the Spo11p is removed to allow subsequent steps in recombination. In strains with the rad50S mutation, however, Spo11p stays covalently attached to the broken DNA ends (11).Coldspots in yeast have received less attention than hotspots. Lambie and Roeder (12) showed that the centromere of chromosome III reduced crossing-over and gene conversion of nearby markers, and Baudat and Nicolas (13) noted a lack of DSB sites near the centromere. Several researchers have found a relative lack of DSB sites in rad50S strains near the telomeres (13,14).Although observations concerning individual hotspots and coldspots have given clues as to the mechanism of recombination initiation, our ability to predict hotspots and coldspots from DNA sequence information is very limited. A complementary approach is to map hotspots and coldspots globally and to determine whether they share common DNA sequences and͞or structural elements. Such mapping studies have been performed to map DSB sites to single-gene resolution on chromosome III (13) and to the resolution of a pulsed-field gel on chromosomes I, III, and VI (14,15). By using DNA samples enriched for meiosis-specific DSBs as hybridization probes on DNA microarrays, we extended these analyses to measure the global distribution of DSBs at single-gene resolution. Materials and MethodsYeast Strains. FX4, FX6, and QFY105 are diploid rad50S strains that have been described (4). These strains (used in the microarray analysis) are isogenic except for changes introduced by transformati...

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Section: Relationship Between Hotspots and Known Repetitive Chromosomalmentioning

confidence: 99%

Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae

Gerton

DeRisi²,

Shroff³

et al. 2000

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

464

517

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“…The molecular basis of this correlation is not clear. Blumental-Perry et al (6) reported that DSBs in S. cerevisiae were correlated with a 50-bp degenerate motif termed the common homology region or CoHR. However, a recent test of this hypothesis found no significant association of the CoHR with DSB sites, and deletion of the CoHR at HIS2, one of the hot spots used to identify the CoHR sequence, affected neither the position nor the intensity of meiotic DNA breakage at that site (19).…”

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confidence: 99%

Natural Meiotic Recombination Hot Spots in the Schizosaccharomyces pombe Genome Successfully Predicted from the Simple Sequence Motif M26

Steiner

Smith

2005

Molecular and Cellular Biology

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The M26 hot spot of meiotic recombination in Schizosaccharomyces pombe is the eukaryotic hot spot most thoroughly investigated at the nucleotide level. The minimum sequence required for M26 activity was previously determined to be 5-ATGACGT-3. Originally identified by a mutant allele, ade6-M26, the M26 heptamer sequence occurs in the wild-type S. pombe genome approximately 300 times, but it has been unclear whether any of these are active hot spots. Recently, we showed that the M26 heptamer forms part of a larger consensus sequence, which is significantly more active than the heptamer alone. We used this expanded sequence as a guide to identify a smaller number of sites most likely to be active hot spots. Ten of the 15 sites tested showed meiotic DNA breaks, a hallmark of recombination hot spots, within 1 kb of the M26 sequence. Among those 10 sites, one occurred within a gene, cds1؉ , and hot spot activity of this site was confirmed genetically. These results are, to our knowledge, the first demonstration in any organism of a simple, defined nucleotide sequence accurately predicting the locations of natural meiotic recombination hot spots. M26 may be the first example among a diverse group of simple sequences that determine the distribution, and hence predictability, of meiotic recombination hot spots in eukaryotic genomes.Homologous recombination occurs at high frequency during meiosis in most sexually reproducing organisms (4). Crossovers resulting from recombination create connections between homologous chromosomes (chiasmata), which are critical for the proper segregation of chromosomes at the first meiotic division. In the absence of recombination, homologs segregate nearly randomly in most organisms, often resulting in aneuploid meiotic products (gametes or spores). Aneuploid progeny in multicellular eukaryotes, such as humans, are usually inviable or suffer from a number of physical and mental abnormalities, as seen, for example, in human trisomy 21 (Down syndrome). In addition to its role in the proper segregation of chromosomes, meiotic recombination also results in the formation of new genetic combinations and is therefore an important mechanism of increasing genetic diversity within a species.Recombination does not occur at a uniform frequency throughout the genomes of the organisms examined. Rather, there are sites that recombine at a significantly higher or lower frequency than the genomic average, termed hot spots and cold spots, respectively. Hot spots have been described in organisms as diverse as bacteria and their phages, mice, and humans (9, 26, 30). In the two distantly related yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, meiotic hot spots of recombination are sites of programmed double-strand DNA breaks (DSBs) made by the Spo11 protein (Rec12 in S. pombe) (11,26,31,33). Spo11 is a meiotically induced protein with amino acid sequence similarity to an archaeal type II topoisomerase, TopoVI. Spo11 homologs are widely conserved in eukaryotes and are essential for meiotic recom...

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“…There may be additional types of hotspots. For example, another genomewide analysis identified a 50-bp region with a poly(A) tract at its center, termed a ''CoHR,'' that has a high degree of correlation with known double-strand break sites (16). At HIS4, the transcription factors Rap1p, Bas1p, and Bas2p͞Pho2p bind upstream of the ORF (17)(18)(19) and stimulate gene conversion 2-to 3-fold (13,14,20).…”

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confidence: 99%

Meiotic recombination frequencies are affected by nutritional states in Saccharomyces cerevisiae

Abdullah

Borts

2001

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

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Meiotic recombination in the yeast Saccharomyces cerevisiae is initiated by programmed double-strand breaks at selected sites throughout the genome (hotspots). ␣-Hotspots are binding sites for transcription factors. Double-strand breaks at ␣-hotspots require binding of transcription factor but not high levels of transcription per se. We show that modulating the production of the transcription factor Gcn4p by deletion or constitutive transcription alters the rate of gene conversion and crossing-over at HIS4. In addition, we show that alterations in the metabolic state of the cell change the frequency of gene conversion at HIS4 in a Gcn4p-dependent manner. We suggest that recombination data obtained from experiments using amino acid and other biosynthetic genes for gene disruptions and͞or as genetic markers should be treated cautiously. The demonstration that Gcn4p affects transcription of more than 500 genes and that the recombinationally ''hottest'' ORFs tend to be Gcn4p-regulated suggest that the metabolic state of a cell, especially with respect to nitrogen metabolism, is a determinant of recombination rates. This observation suggests that the effects of metabolic state may be global and may account for some as yet unexplained features of recombination in higher organisms, such as the differences in map length between the sexes.

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DNA motif associated with meiotic double‐strand break regions in Saccharomyces cerevisiae

Cited by 21 publications

References 25 publications

Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae

Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae

Natural Meiotic Recombination Hot Spots in the Schizosaccharomyces pombe Genome Successfully Predicted from the Simple Sequence Motif M26

Meiotic recombination frequencies are affected by nutritional states in Saccharomyces cerevisiae

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