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Reference - PMID:15654094 - A novel recombination pathway initiated by the Mre11/Rad50/Nbs1 complex eliminates palindromes during meiosis in Schizosaccharomyces pombe.

Reference summary

PubMed ID
PMID:15654094
Title
A novel recombination pathway initiated by the Mre11/Rad50/Nbs1 complex eliminates palindromes during meiosis in Schizosaccharomyces pombe.
Authors
Farah JA, Cromie G, Steiner WW, Smith GR
Citation
Genetics 2005 Mar;169(3):1261-74
Publication year
2005
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.

Annotation

GO biological process

GO:0042138 - meiotic DNA double-strand break formation

Genes:

GO:0007131 - reciprocal meiotic recombination

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Multi-locus phenotype

FYPO:0003179 - decreased intragenic meiotic recombination

Genes:

Genotypes:

FYPO:0005433 - decreased meiotic recombination at hotspot

Genes:

Genotypes:

FYPO:0000581 - decreased spore germination frequency

Genes:

Genotypes:

FYPO:0005434 - globally decreased meiotic recombination

Genes:

Genotypes:

Single locus phenotype

FYPO:0003564 - abnormal meiotic DNA double-strand break formation

Genes:

Genotypes:

FYPO:0005433 - decreased meiotic recombination at hotspot

Genes:

Genotypes:

FYPO:0000581 - decreased spore germination frequency

Genes:

Genotypes:

FYPO:0005434 - globally decreased meiotic recombination

Genes:

Genotypes:

FYPO:0004059 - normal meiotic recombination at CRE promoter

Genes:

Genotypes: