Reference - PMID:18566005 - Structural and functional analyses of the DMC1-M200V polymorphism found in the human population.
Reference summary
- PubMed ID
- PMID:18566005
- Title
- Structural and functional analyses of the DMC1-M200V polymorphism found in the human population.
- Authors
- Hikiba J, Hirota K, Kagawa W, Ikawa S, Kinebuchi T, Sakane I, Takizawa Y, Yokoyama S, Mandon-Pépin B, Nicolas A, Shibata T, Ohta K, Kurumizaka H
- Citation
- Nucleic Acids Res 2008 Jul;36(12):4181-90
- Publication year
- 2008
- Abstract
- The M200V polymorphism of the human DMC1 protein, which is an essential, meiosis-specific DNA recombinase, was found in an infertile patient, raising the question of whether this homozygous human DMC1-M200V polymorphism may cause infertility by affecting the function of the human DMC1 protein. In the present study, we determined the crystal structure of the human DMC1-M200V variant in the octameric-ring form. Biochemical analyses revealed that the human DMC1-M200V variant had reduced stability, and was moderately defective in catalyzing in vitro recombination reactions. The corresponding M194V mutation introduced in the Schizosaccharomyces pombe dmc1 gene caused a significant decrease in the meiotic homologous recombination frequency. Together, these structural, biochemical and genetic results provide extensive evidence that the human DMC1-M200V mutation impairs its function, supporting the previous interpretation that this single-nucleotide polymorphism is a source of human infertility.
