Genetics. Published Articles Ahead of Print: January 16, 2005, Copyright © 2005
doi:10.1534/genetics.104.037515


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

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A novel recombination pathway initiated by the MRN complex eliminates palindromes during meiosis in Schizosaccharomyces pombe

Joseph A. Farah 1, Gareth Cromie 1, Walter W. Steiner 2 and Gerald R. Smith 3*

1 Fred HutchinsonCancer Research Center
2 Niagara University
3 Fred Hutchinson Cancer Research Center

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

Submitted on October 12, 2004
Revised on November 11, 2004
Accepted on 22 November 2004


Abstract

DNA palindromes are rare in humans but are associated with meiosis-specific transloca-tions. The conserved Mre11•Rad50•Nbs1 (MRN) complex is likely directly involved in processing palindromes through the homologous recombination pathway of DNA repair. Using the fission yeast Schizosaccharomyces pombe as a model system, we show that a 160 bp palindrome (M-pal) is a meiotic recombination hotspot and is preferentially eliminated by gene conversion. Importantly, this hotspot depends on the MRN complex for full activity and reveals a new pathway for generating meiotic DNA double-strand breaks (DSBs), separate from the Rec12 (ortholog of Spo11) pathway. We show that MRN-dependent DSBs are formed at or near the M-pal in vivo, and in contrast to the Rec12-dependent breaks, they appear early, during premeiotic replication. Analysis of mrn mutants indicates that the early DSBs are generated by the MRN nuclease activity, demonstrating the previously hypothesized MRN-dependent breakage of hairpins during replication. Our studies provide a genetic and physical basis for frequent translocations between palindromes in human meiosis and identify a conserved meiotic process that constantly selects against palindromes in eukaryotic genomes.

Key Words: S. pombe, DNA palindrome, MRN complex, Meiotic recombination hotspot, Spo11




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