title: Chromatin architecture may dictate the target site for DMC1, but not for RAD51, during homologous pairing.
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.
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science &Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science &Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Takaku
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science &Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Machida
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science &Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tachiwana
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Maehara
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science &Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.|Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006657:Histones / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes; D004247:DNA; D051135:Rad51 Recombinase; C074556:DMC1 protein, human