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Protein determinants of meiotic DNA break hot spots.

ABSTRACT: Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to hundreds of times more frequently at special sites, called hot spots, than in other regions of the genome. What distinguishes hot spots from cold regions is an unsolved problem, although transcription factors determine some hot spots. We report the discovery that three coiled-coil proteins-Rec25, Rec27, and Mug20-bind essentially all hot spots with great specificity even without DSB formation. These small proteins are components of linear elements, are related to synaptonemal complex proteins, and are essential for nearly all DSBs at most hot spots. Our results indicate these hot spot determinants activate or stabilize the DSB-forming protein Rec12 (Spo11 homolog) rather than promote its binding to hot spots. We propose a paradigm for hot spot determination and crossover control by linear element proteins.

SUBMITTER: Fowler KR

PROVIDER: S-EPMC3595357 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Protein determinants of meiotic DNA break hot spots.

Fowler Kyle R KR Gutiérrez-Velasco Susana S Martín-Castellanos Cristina C Smith Gerald R GR

Molecular cell 20130207 5

Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to hundreds of times more frequently at special sites, called hot spots, than in other regions of the genome. What distinguishes hot spots from cold regions is an unsolved problem, although transcription factors determine some hot spots. We report the discovery that ...[more]

PMID: 23395004

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Project description:BackgroundMeiotic recombination events have been found to concentrate in 1-2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Some previous evidence suggests that poly-purine/poly-pyrimidine (poly-pu/py) tracts (PPTs), a class of sequence with distinctive biochemical properties, could be involved in recombination, but no general association of PPTs with meiotic recombination hot spots has previously been reported.ResultsWe used computational methods to investigate in detail the relationship between PPTs and hot spots. We show statistical associations of PPT frequency with hot spots of meiotic recombination initiating lesions, double-strand breaks, in the genome of the yeast S. cerevisiae and with experimentally well characterized human meiotic recombination hot spots. Supporting a possible role of poly-pu/py-rich sequences in hot spot recombination, we also found that all three single nucleotide polymorphisms previously shown to be associated with human hot spot activity changes occur within sequence contexts of 14 bp or longer that are 85% or more poly-pu/py and at least 70% G/C. These polymorphisms are all close to the hot spot mid points. Comparing the sequences of experimentally characterized human hot spots with the orthologous regions of the chimpanzee genome previously shown not to contain hot spots, we found that in all five cases in which comparisons for the hot spot central regions are possible with publicly available sequence data, there are differences near the human hot spot mid points within sequences 14 bp or longer consisting of more than 80% poly-pu/py and at least 50% G/C.ConclusionOur results, along with previous evidence for the unique biochemical properties and recombination-stimulating potential of poly-pu/py-rich sequences, suggest that the possible functional involvement of this type of sequence in meiotic recombination hot spots deserves further experimental exploration.

Dataset Information

Protein determinants of meiotic DNA break hot spots.

Publications

Protein determinants of meiotic DNA break hot spots.

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