A novel recombination pathway initiated by the Mre11/Rad50/Nbs1 complex eliminates palindromes during meiosis in Schizosaccharomyces pombe.
DNA palindromes are rare in humans but are associated with meiosis-specific translocations. 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), separately 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.
Farah
Joseph A
JA
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Cromie
Gareth
G
Steiner
Walter W
WW
Smith
Gerald R
GR
D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D017124:Conserved Sequence; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics*; D005819:Genetic Markers; D008540:Meiosis / Q000235:genetics; D008957:Models, Genetic; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000235:genetics* / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D005819:Genetic Markers; C478035:Nbs1 protein, S pombe; C480032:Rad50 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins