title: Biochemical analysis of the human DMC1-I37N polymorphism.
abstract: The DMC1 protein, a meiosis-specific DNA recombinase, promotes homologous pairing and strand exchange. The I37N single nucleotide polymorphism of the human DMC1 protein was reported as a result of human genome sequencing projects. In this study, we purified the human DMC1-I37N variant, as a recombinant protein. The DMC1 protein is known to require DNA for efficient ATP hydrolysis. By contrast, the DMC1-I37N variant efficiently hydrolyzed ATP in the absence of DNA. Like the conventional DMC1 protein, the DMC1-I37N variant promoted strand exchange, but it required a high Ca2+ concentration (4-8 mm), a condition that inactivates the strand-exchange activity of the conventional DMC1 protein. These biochemical differences between the DMC1 and DMC1-I37N proteins suggest that the DMC1-I37N polymorphism may be a source of improper meiotic recombination, causing meiotic defects in humans.
authors.affiliation: Laboratory of Structural Biology, Waseda University, Tokyo, Japan.
authors.forename: Juri
authors.initials: J
authors.lastname: Hikiba
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takizawa
authors.forename: Shukuko
authors.initials: S
authors.lastname: Ikawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Shibata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001669:Biochemical Phenomena; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011485:Protein Binding
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D000251:Adenosine Triphosphatases; C074556:DMC1 protein, human