Determinants of recombination activity?the alternative hotspot view
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European Society of Evolutionary Biology
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Meiotic recombination, necessary for sexual reproduction, is localized in most higher-order organisms in recombination hotspots. Recent advances of mapping genome-wide recombination hotspots at a very fine scale have highlighted the importance of trans-acting factors like PRDM9 in establishing hotspot locations in most mammals. PRDM9 is a meiosis-specific, multi-domain protein that regulates the location of recombination hotspots by targeting its DNA recognition motifs for double strand breaks (DSBs). However, we still do not fully understand the role of this protein in hotspot determination. Thus, we investigated the binding nature of PRDM9 by in vitro methods and determined that the PRDM9 zinc finger domain forms a highly stable complex with its recognition motif, and polymorphisms in the recognition sequence directly affect the binding affinity of PRDM9. Thus, given the rapid sequence evolution of DNA at hotspots due to conversions and mutations, PRDM9 binding becomes weaker with time, as well as its associated recombination activity. We also investigated the role of poly-As in recombination and observed a reduction in crossing-over and potential shift in the crossover distribution for donors polymorphic for polyAs located at the center of a hotspot. Our data suggest that poly-As influences recombination in a PRDM9-independent manner.
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