Models of Recombination

His

7

1

+

+

+

+thr

arg

Fogel and Hurst. 1967. Meiotic gene conversion in yeast tetrads and the theory of recombination. Genetics. 57: 455-481.

None

Region I

Region II

Regions I & II

70

5

0

1

-

2

0

1

Reciprocal crossing over between sites 7 and 1

None

Region I

Region II

Regions I & II

220

141

84

7

-

138

60

7

Conversion of site 7 to +

None

Region I

Region II

Regions I & II

23

3

49

0

-

3

49

0

Conversion of site 1 to +

Events leading to His+

tetrads w. crossovers

in:

Nos. of tetrads

Nos. of tetrads in which the His+ strand participates in a

crossover

Summary: gene conversion:

• Replacement of one allele by another on a non-sister chromatid, leading to “abnormal” segregation ratios in tetrads.

• In about half the cases in which gene conversion occurs, there is also full (i.e., reciprocal crossing over between flanking markers. The conversion site itself must be involved in the process of crossing over.

• Models of recombination must account for gene conversion and its association with crossing over as observed in yeast tetrads.

Models of recombination

• Initiation by nicking of DNA• Exchange of single nucleotide strands between chromatids (DNA duplexes), which creates heteroduplexed areas.

• Mismatch repair of heteroduplexes or not.

• Resolution of the intermediate (reciprocal recomnination for flanking makers, or not).

(a) pair of chromatids

(b) a single strand cut is made in each chromatid

(c) strand exchange takes place between the chromatids

(d) ligation occurs yielding two completely intact DNA molecules

The Holliday model

(e) Branch migration occurs, giving regions of heteroduplex DNA

(f) Resolution of the Holliday junction gives two DNA molecules with heteroduplex DNA. Depending upon how the Holliday junction is resolved, we either observe no exchange of flanking markers (left) or an exchange of flanking markers (right)

If the heteroduplex is repaired, the result is either a chromatid conversion or a normal chromatid, depending on which allele is removed.

If the heteroduplex is not repaired, then when the resulting DNA replicates, one daughter DNA molecular is +, while the other DNA molecular is m. The result is a half-chromatid conversion wherein only half the chromatid is converted.

Summary of the Holliday model

• Single-strand DNA nick on both chromatids.

• Strand exchange generates the Holliday junction.

A Modification of the Holliday Model:

The Meselson-Radding model

• A single DNA strand is nicked.• Strand displacement (invasions) and subsequent DNA synthesis generates the Holliday junction

The Meselson-Radding model

The Meselson-Radding model

Double-Strand Break-Repair model

• A single double-strand break is generated in one chromatid (DNA molecule)

• Strand displacement (invasion) and subsequent DNA synthesis generates the Holliday junction.

Double-Strand Break-Repair model

Double-Strand Break-Repair model

Proc. Natl. Acad. Sci. USAVol. 94, pp. 5213-5218, May 1997

Genetics

Clustering of meiotic double-strand breaks on yeast chromosome III

Frédéric Baudat and Alain Nicolas*

Institut Curie, Section de Recherche, Centre National de la Recherche Scientifique, Unité Mixte deRecherche 144, Compartimentation et Dynamique Cellulaires, 26 rue d'Ulm, 75248

Paris Cedex 05, France

ABSTRACT

In the yeast Saccharomyces cerevisiae, meiotic recombination is initiated by transient DNA double-strand breaks (DSBs) that are repaired by interaction of the broken chromosome with its homologue. To identify a large number of DSB sites and gain insight into the control of DSB formation at both the local and the whole chromosomal levels, we have determined at high resolution the distribution of meiotic DSBs along the 340 kb of chromosome III. We have found 76 DSB regions, mostly located in intergenic promoter-containing intervals. The frequency of DSBs varies at least 50-fold from one region to another. The global distribution of DSB regions along chromosome III is nonrandom, defining large (39-105 kb) chromosomal domains, both hot and cold. The distribution of these localized DSBs indicates that they are likely to initiate most crossovers along chromosome III, but some discrepancies remain to be explained.

Figure 2. Location and amount of meiotic DSBs on chromosome III.