A novel recombination pathway initiated by the Mre11/Rad50/Nbs1 complex eliminates palindromes during meiosis in Schizosaccharomyces pombe

Genetics. 2005 Mar;169(3):1261-74. doi: 10.1534/genetics.104.037515. Epub 2005 Jan 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Chromosomal Proteins, Non-Histone / genetics*
  • Conserved Sequence
  • DNA Damage
  • DNA Repair
  • DNA, Fungal / chemistry
  • DNA, Fungal / genetics*
  • Genetic Markers
  • Meiosis / genetics
  • Models, Genetic
  • Recombination, Genetic*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / growth & development
  • Schizosaccharomyces pombe Proteins / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • Genetic Markers
  • Nbs1 protein, S pombe
  • Rad50 protein, S pombe
  • Schizosaccharomyces pombe Proteins