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Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination

Hyun-Ah Kang1, Ho-Chul Shin2, Alexandra-Styliani Kalantzi3

  • 1Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

Nucleic Acids Research
|March 6, 2015
PubMed

Insights

The Hop2-Mnd1 complex facilitates DNA recombination by helping Dmc1-mediated strand invasion. Its structure reveals how it interacts with DNA to promote this crucial step in meiosis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Structural Biology

Background:

  • Meiotic DNA recombination is essential for accurate chromosome segregation.
  • The Hop2-Mnd1 complex is known to promote Dmc1-mediated strand invasion, but its mechanism remains unclear.

Purpose of the Study:

  • To elucidate the structural basis of Hop2-Mnd1 function in promoting Dmc1-mediated strand invasion during meiotic recombination.

Main Methods:

  • Crystal structure determination of the Hop2-Mnd1 complex.
  • Deletion analysis to identify functional domains.
  • Molecular modeling and simulations to understand interactions with DNA and Dmc1.

Main Results:

  • Hop2-Mnd1 forms a curved, rod-like structure with distinct functional domains: a helical bundle interacting with Dmc1-ssDNA and winged-helix domains potentially perturbing dsDNA base pairing.
  • The helical bundle is sufficient for Dmc1-ssDNA nucleofilament interaction.
  • Molecular modeling suggests the rod fits into the nucleofilament groove.

Conclusions:

  • A structural model is proposed where Hop2-Mnd1 juxtaposes Dmc1-bound ssDNA with distorted dsDNA, facilitating strand invasion.
  • The findings provide mechanistic insights into Hop2-Mnd1's role in homologous chromosome pairing and recombination.

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