Genetics. Published Articles Ahead of Print: November 15, 2004, Copyright © 2004
doi:10.1534/genetics.104.037176


A more recent version of this article appeared on February 1, 2005.


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A Natural Meiotic DNA Break Site in Schizosaccharomyces pombe is a Hotspot of Gene Conversion, Highly Associated with Crossing-over

1 Fred Hutchinson Cancer Research Center

* To whom correspondence should be addressed. E-mail: gsmith{at}fhcrc.org.

Submitted on October 5, 2004
Revised on October 31, 2004
Accepted on 9 November 2004


Abstract

In Schizosaccharomyces pombe meiosis-specific DNA breaks that initiate recombination are observed at prominent but widely separated sites. We investigated the relationship between breakage and recombination at one of these sites, the mbs1 locus on chromosome I. A total of 10% breakage was mapped to four clusters spread over a 2.1 kb region. Gene conversion of markers within the clusters occurred in 3% of meiotic chromatids (11% of tetrads), making mbs1 a conversion hotspot compared to other fission yeast markers. Approximately 80% of these conversions were associated with crossing-over of flanking markers, suggesting strong bias in meiotic break repair towards the generation of crossovers. This bias was observed in conversion events at three other loci, ade6, ade7 and ura1. 50-80% of all crossovers seen in a 90 kb region flanking mbs1 occurred in a 4.8 kb interval containing the break sites. Thus, mbs1 is also a hotspot of crossing-over, with breakage at mbs1 generating most of the crossovers in the 90 kb interval. Neither Rec12 (Spo11 ortholog) nor I-SceI-induced breakage at mbs1 was significantly associated with crossing-over in an apparently break-free interval >25 kb away. Possible mechanisms for generating crossovers in such break-free intervals are discussed.

Key Words: DNA breaks, Schizosaccharomyces pombe, crossing-over, gene conversion, meiotic recombination hotspot




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