Abstract
In eukaryotes, genomic DNA is compacted as chromatin, in which histones and DNA form the nucleosome as the basic unit. DMC1 and RAD51 are essential eukaryotic recombinases that mediate homologous chromosome pairing during homologous recombination. However, the means by which these two recombinases distinctly function in chromatin have remained elusive. Here we found that, in chromatin, the human DMC1-single-stranded DNA complex bypasses binding to the nucleosome, and preferentially promotes homologous pairing at the nucleosome-depleted regions. Consistently, DMC1 forms ternary complex recombination intermediates with the nucleosome-free DNA or the nucleosome-depleted DNA region. Surprisingly, removal of the histone tails improperly enhances the nucleosome binding by DMC1. In contrast, RAD51 does not specifically target the nucleosome-depleted region in chromatin. These are the first demonstrations that the chromatin architecture specifies the sites to promote the homologous recombination reaction by DMC1, but not by RAD51.
Highlights
In eukaryotes, genomic DNA is compacted as chromatin, in which histones and DNA form the nucleosome as the basic unit
In meiotic cell division I, homologous recombination occurs between homologous chromosomes in the synaptonemal complex, and plays essential roles in chiasma formation
Bugreev et al made the important discovery that RAD51 is swiftly removed from the recombination site after homologous pairing, but DMC1 is resistant to dissociation from the homologous pairing products[44]
Summary
Genomic DNA is compacted as chromatin, in which histones and DNA form the nucleosome as the basic unit. Meiotic DSBs are reportedly introduced on the chromatin loop regions that transiently interact with the lateral elements of the synaptonemal complex[7,8,9,10], suggesting that these chromatin regions may contain nucleosome-depleted regions Some of these DSB sites are hot spots for meiotic homologous recombination between homologous chromosomes. In yeasts, these meiotic recombination hot spots are generally open chromatin structures containing nucleosome-depleted regions, where the SPO11 that is transiently associated with the lateral elements can access the DNA10–14. The DMC1-ssDNA or RAD51-ssDNA complex is bound to the dsDNA target, and the homologous DNA sequences are aligned within the ternary complex containing ssDNA, dsDNA, and DMC1 or RAD51
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