Competition Between Adjacent Meiotic Recombination Hotspots in the Yeast Saccharomyces cerevisiae

Abstract Meiotic recombination is one of the most important driving forces of biological evolution, which is initiated by double-strand DNA breaks. Recombination has important roles in genome diversity and evolution. This review firstly provides a comprehensive survey of the 15 computational methods developed for identifying recombination hotspots in Saccharomyces cerevisiae. These computational methods were discussed and compared in terms of underlying algorithms, extracted features, predictive capability and practical utility. Subsequently, a more objective benchmark data set was constructed to develop a new predictor iRSpot-Pse6NC2.0 (http://lin-group.cn/server/iRSpot-Pse6NC2.0). To further demonstrate the generalization ability of these methods, we compared iRSpot-Pse6NC2.0 with existing methods on the chromosome XVI of S. cerevisiae. The results of the independent data set test demonstrated that the new predictor is superior to existing tools in the identification of recombination hotspots. The iRSpot-Pse6NC2.0 will become an important tool for identifying recombination hotspot.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.97.21.11383 ◽

2000 ◽

Vol 97 (21) ◽

pp. 11383-11390 ◽

Cited By ~ 328

Author(s):

J. L. Gerton ◽

J. DeRisi ◽

R. Shroff ◽

M. Lichten ◽

P. O. Brown ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Meiotic Recombination ◽

Yeast Saccharomyces Cerevisiae ◽

Recombination Hotspots ◽

Global Mapping ◽

Meiotic Recombination Hotspots

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Measurements of excision repair tracts formed during meiotic recombination in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.12.4.1805-1814.1992 ◽

1992 ◽

Vol 12 (4) ◽

pp. 1805-1814

Author(s):

P Detloff ◽

T D Petes

Keyword(s):

Saccharomyces Cerevisiae ◽

Meiotic Recombination ◽

High Frequency ◽

Excision Repair ◽

Yeast Saccharomyces Cerevisiae ◽

Heteroduplex Dna ◽

Homologous Chromosomes ◽

His4 Gene

During meiotic recombination in the yeast Saccharomyces cerevisiae, heteroduplexes are formed at a high frequency between HIS4 genes located on homologous chromosomes. Using mutant alleles of the HIS4 gene that result in poorly repaired mismatches in heteroduplex DNA, we find that heteroduplexes often span a distance of 1.8 kb. In addition, we show that about one-third of the repair tracts initiated at well-repaired mismatches extend 900 bp.

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Measurements of excision repair tracts formed during meiotic recombination in Saccharomyces cerevisiae.

Molecular and Cellular Biology ◽

10.1128/mcb.12.4.1805 ◽

1992 ◽

Vol 12 (4) ◽

pp. 1805-1814 ◽

Cited By ~ 22

Author(s):

P Detloff ◽

T D Petes

Keyword(s):

Saccharomyces Cerevisiae ◽

Meiotic Recombination ◽

High Frequency ◽

Excision Repair ◽

Yeast Saccharomyces Cerevisiae ◽

Heteroduplex Dna ◽

Homologous Chromosomes ◽

His4 Gene

During meiotic recombination in the yeast Saccharomyces cerevisiae, heteroduplexes are formed at a high frequency between HIS4 genes located on homologous chromosomes. Using mutant alleles of the HIS4 gene that result in poorly repaired mismatches in heteroduplex DNA, we find that heteroduplexes often span a distance of 1.8 kb. In addition, we show that about one-third of the repair tracts initiated at well-repaired mismatches extend 900 bp.

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Meiotic Recombination Involving Heterozygous Large Insertions inSaccharomyces cerevisiae: Formation and Repair of Large, Unpaired DNA Loops

Genetics ◽

10.1093/genetics/158.4.1457 ◽

2001 ◽

Vol 158 (4) ◽

pp. 1457-1476 ◽

Cited By ~ 5

Author(s):

Hutton M Kearney ◽

David T Kirkpatrick ◽

Jennifer L Gerton ◽

Thomas D Petes

Keyword(s):

Saccharomyces Cerevisiae ◽

Meiotic Recombination ◽

Excision Repair ◽

Large Bubble ◽

Dna Breaks ◽

Double Strand Dna Breaks ◽

Dna Loop ◽

Nucleotide Excision ◽

Dna Strands ◽

Mmr Proteins

AbstractMeiotic recombination in Saccharomyces cerevisiae involves the formation of heteroduplexes, duplexes containing DNA strands derived from two different homologues. If the two strands of DNA differ by an insertion or deletion, the heteroduplex will contain an unpaired DNA loop. We found that unpaired loops as large as 5.6 kb can be accommodated within a heteroduplex. Repair of these loops involved the nucleotide excision repair (NER) enzymes Rad1p and Rad10p and the mismatch repair (MMR) proteins Msh2p and Msh3p, but not several other NER (Rad2p and Rad14p) and MMR (Msh4p, Msh6p, Mlh1p, Pms1p, Mlh2p, Mlh3p) proteins. Heteroduplexes were also formed with DNA strands derived from alleles containing two different large insertions, creating a large “bubble”; repair of this substrate was dependent on Rad1p. Although meiotic recombination events in yeast are initiated by double-strand DNA breaks (DSBs), we showed that DSBs occurring within heterozygous insertions do not stimulate interhomologue recombination.

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Genetic evidence that the meiotic recombination hotspot at the HIS4 locus of Saccharomyces cerevisiae does not represent a site for a symmetrically processed double-strand break.

Genetics ◽

10.1093/genetics/134.1.5 ◽

1993 ◽

Vol 134 (1) ◽

pp. 5-19 ◽

Cited By ~ 5

Author(s):

S E Porter ◽

M A White ◽

T D Petes

Keyword(s):

Saccharomyces Cerevisiae ◽

Binding Site ◽

Meiotic Recombination ◽

Strand Break ◽

Yeast Saccharomyces Cerevisiae ◽

Recombination Hotspot ◽

Dna Break ◽

A Site ◽

Aberrant Segregation ◽

His4 Gene

Abstract In the yeast Saccharomyces cerevisiae, the binding of the Rap1 protein to a site located between the 5' end of the HIS4 gene and the 3' end of BIK1 stimulates meiotic recombination at both flanking loci. By using strains that contain mutations located in HIS4 and BIK1, we found that most recombination events stimulated by the binding of Rap1 involve HIS4 or BIK1, rather than bidirectional events including both loci. The patterns of aberrant segregation indicate that most of the Rap1-stimulated recombination events do not represent the symmetric processing of a double-strand DNA break located at the Rap1-binding site.

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Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: control in cis and trans.

Molecular and Cellular Biology ◽

10.1128/mcb.15.3.1679 ◽

1995 ◽

Vol 15 (3) ◽

pp. 1679-1688 ◽

Cited By ~ 76

Author(s):

Q Fan ◽

F Xu ◽

T D Petes

Keyword(s):

Saccharomyces Cerevisiae ◽

Hot Spot ◽

Wild Type ◽

Dna Breaks ◽

Yeast Saccharomyces Cerevisiae ◽

Double Strand Dna Breaks ◽

Spot Activity ◽

Chromosome Iii ◽

High Level ◽

Double Strand Dna

The region of Saccharomyces cerevisiae chromosome III located between the 5' end of the HIS4 gene and the 3' end of the adjacent BIK1 gene has a very high level of meiotic recombination. In wild-type strains, a meiosis-specific double-strand DNA break occurs in the hot spot region. This break is absent in strains in which the transcription factors Rap1p, Bas1p, and Bas2p cannot bind to the region upstream of HIS4. In strains with levels of recombination that are higher than those of the wild type, the break is found at elevated levels. The linear relationship between hot spot activity and the frequency of double-strand DNA breaks suggests that these lesions are responsible for initiating recombination at the HIS4 recombination hot spot.

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Global Analysis of the Relationship between the Binding of the Bas1p Transcription Factor and Meiosis-Specific Double-Strand DNA Breaks in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.26.3.1014-1027.2006 ◽

2006 ◽

Vol 26 (3) ◽

pp. 1014-1027 ◽

Cited By ~ 50

Author(s):

Piotr A. Mieczkowski ◽

Margaret Dominska ◽

Michael J. Buck ◽

Jennifer L. Gerton ◽

Jason D. Lieb ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Transcription Factor ◽

Meiotic Recombination ◽

Binding Sites ◽

Hot Spot ◽

Wild Type ◽

Dna Breaks ◽

Recombination Activity ◽

Double Strand Dna Breaks ◽

Spot Activity

ABSTRACT In the yeast Saccharomyces cerevisiae, certain genomic regions have very high levels of meiotic recombination (hot spots). The hot spot activity associated with the HIS4 gene requires the Bas1p transcription factor. To determine whether this relationship between transcription factor binding and hot spot activity is general, we used DNA microarrays to map all genomic Bas1p binding sites and to map the frequency of meiosis-specific double-strand DNA breaks (as an estimate of the recombination activity) of all genes in both wild-type and bas1 strains. We identified sites of Bas1p-DNA interactions upstream of 71 genes, many of which are involved in histidine and purine biosynthesis. Our analysis of recombination activity in wild-type and bas1 strains showed that the recombination activities of some genes with Bas1p binding sites were dependent on Bas1p (as observed for HIS4), whereas the activities of other genes with Bas1p binding sites were unaffected or were repressed by Bas1p. These data demonstrate that the effect of transcription factors on meiotic recombination activity is strongly context dependent. In wild-type and bas1 strains, meiotic recombination was strongly suppressed in large (25- to 150-kb) chromosomal regions near the telomeres and centromeres and in the region flanking the rRNA genes. These results argue that both local and regional factors affect the level of meiotic recombination.

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Factors that affect the location and frequency of meiosis-induced double-strand breaks in Saccharomyces cerevisiae.

Genetics ◽

10.1093/genetics/140.1.55 ◽

1995 ◽

Vol 140 (1) ◽

pp. 55-66 ◽

Cited By ~ 6

Author(s):

T C Wu ◽

M Lichten

Keyword(s):

Saccharomyces Cerevisiae ◽

Chromatin Structure ◽

Meiotic Recombination ◽

Double Strand Breaks ◽

Yeast Genome ◽

Dna Breaks ◽

Strand Breaks ◽

Double Strand Dna Breaks ◽

A Site ◽

Chromosomal Sequences

Abstract Double-strand DNA breaks (DSBs) initiate meiotic recombination in Saccharomyces cerevisiae. DSBs occur at sites that are hypersensitive in nuclease digests of chromatin, suggesting a role for chromatin structure in determining DSB location. We show here that the frequency of DSBs at a site is not determined simply by DNA sequence or by features of chromatin structure. An arg4-containing plasmid was inserted at several different locations in the yeast genome. Meiosis-induced DSBs occurred at similar sites in pBR322-derived portions of the construct at all insert loci, and the frequency of these breaks varied in a manner that mirrored the frequency of meiotic recombination in the arg4 portion of the insert. However, DSBs did not occur in the insert-borne arg4 gene at a site that is frequently broken at the normal ARG4 locus, even though the insert-borne arg4 gene and the normal ARG4 locus displayed similar DNase I hypersensitivity patterns. Deletions that removed active DSB sites from an insert at HIS4 restored breaks to the insert-borne arg4 gene and to a DSB site in flanking chromosomal sequences. We conclude that the frequency of DSB at a site can be affected by sequences several thousand nucleotides away and suggest that this is because of competition between DSB sites for locally limited factors.

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Fine-Structure Mapping of Meiosis-Specific Double-Strand DNA Breaks at a Recombination Hotspot Associated With an Insertion of Telomeric Sequences Upstream of the HIS4 Locus in Yeast

Genetics ◽

10.1093/genetics/143.3.1115 ◽

1996 ◽

Vol 143 (3) ◽

pp. 1115-1125 ◽

Cited By ~ 3

Author(s):

Fei Xu ◽

Thomas D Petes

Keyword(s):

Meiotic Recombination ◽

Hydroxyl Groups ◽

Sequence Specificity ◽

Structure Mapping ◽

Dna Breaks ◽

Exonuclease Iii ◽

Recombination Hotspot ◽

Telomeric Sequences ◽

Double Strand Dna Breaks ◽

Double Strand Dna

Abstract Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upstream of HIS4. We found that the breaks have no obvious sequence specificity and localize to a region of ~50 bp adjacent to the telomeric insertion. By mapping the breaks and by studies of the exonuclease III sensitivity of the broken ends, we conclude that most of the broken DNA molecules have blunt ends with 3′-hydroxyl groups.

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