Activation of human meiosis-specific recombinase Dmc1 by Ca2+

J Biol Chem. 2005 Jul 22;280(29):26886-95. doi: 10.1074/jbc.M502248200. Epub 2005 May 25.


Rad51 and its meiotic homolog Dmc1 are key proteins of homologous recombination in eukaryotes. These proteins form nucleoprotein complexes on single-stranded DNA that promote a search for homology and that perform DNA strand exchange, the two essential steps of genetic recombination. Previously, we demonstrated that Ca2+ greatly stimulates the DNA strand exchange activity of human (h) Rad51 protein (Bugreev, D. V., and Mazin, A. V. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 9988-9993). Here, we show that the DNA strand exchange activity of hDmc1 protein is also stimulated by Ca2+. However, the mechanism of stimulation of hDmc1 protein appears to be different from that of hRad51 protein. In the case of hRad51 protein, Ca2+ acts primarily by inhibiting its ATPase activity, thereby preventing self-conversion into an inactive ADP-bound complex. In contrast, we demonstrate that hDmc1 protein does not self-convert into a stable ADP-bound complex. The results indicate that activation of hDmc1 is mediated through conformational changes induced by free Ca2+ ion binding to a protein site that is distinct from the Mg2+.ATP-binding center. These conformational changes are manifested by formation of more stable filamentous hDmc1.single-stranded DNA complexes. Our results demonstrate a universal role of Ca2+ in stimulation of mammalian DNA strand exchange proteins and reveal diversity in the mechanisms of this stimulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate
  • Binding Sites
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Cell Cycle Proteins / metabolism*
  • Crossing Over, Genetic
  • DNA, Single-Stranded
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Humans
  • Magnesium / pharmacology
  • Meiosis
  • Protein Conformation / drug effects
  • Rad51 Recombinase
  • Recombinases
  • Recombination, Genetic


  • Cell Cycle Proteins
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Recombinases
  • Adenosine Triphosphate
  • RAD51 protein, human
  • Rad51 Recombinase
  • Adenosine Triphosphatases
  • DMC1 protein, human
  • Magnesium
  • Calcium