Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1.
The human Dmc1 protein, a RecA/Rad51 homolog, is a meiosis-specific DNA recombinase that catalyzes homologous pairing. RecA and Rad51 form helical filaments, while Dmc1 forms an octameric ring. In the present study, we crystallized the full-length human Dmc1 protein and solved the structure of the Dmc1 octameric ring. The monomeric structure of the Dmc1 protein closely resembled those of the human and archaeal Rad51 proteins. In addition to the polymerization motif that was previously identified in the Rad51 proteins, we found another hydrogen bonding interaction at the polymer interface, which could explain why Dmc1 forms stable octameric rings instead of helical filaments. Mutagenesis studies identified the inner and outer basic patches that are important for homologous pairing. The inner patch binds both single-stranded and double-stranded DNAs, while the outer one binds single-stranded DNA. Based on these results, we propose a model for the interaction of the Dmc1 rings with DNA.
Kinebuchi
Takashi
T
Protein Research Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
Kagawa
Wataru
W
Enomoto
Rima
R
Tanaka
Kozo
K
Miyagawa
Kiyoshi
K
Shibata
Takehiko
T
Kurumizaka
Hitoshi
H
Yokoyama
Shigeyuki
S
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D008540:Meiosis / Q000235:genetics*; D008958:Models, Molecular; D008970:Molecular Weight; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D017385:Sequence Homology
D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D004247:DNA; D000251:Adenosine Triphosphatases; C074556:DMC1 protein, human