Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
Department of Chemistry, National Taiwan University, Taipei, Taiwan.
Nat Commun. 2024 Oct 27;15(1):9266. doi: 10.1038/s41467-024-53641-3.
Homologous recombination during meiosis is critical for chromosome segregation and also gives rise to genetic diversity. Genetic exchange between homologous chromosomes during meiosis is mediated by the recombinase Dmc1, which is capable of recombining DNA sequences with mismatches. The Hop2-Mnd1 complex mediates Dmc1 activity. Here, we reveal a regulatory role for Hop2-Mnd1 in restricting substrate selection. Specifically, Hop2-Mnd1 upregulates Dmc1 activity with DNA substrates that are either fully homologous or contain DNA mismatches, and it also acts against DNA strand exchange between substrates solely harboring microhomology. By isolating and examining salient Hop2-Mnd1 separation-of-function variants, we show that suppressing illegitimate DNA recombination requires the Dmc1 filament interaction attributable to Hop2-Mnd1 but not its DNA binding activity. Our study provides mechanistic insights into how Hop2-Mnd1 helps maintain meiotic recombination fidelity.
减数分裂过程中的同源重组对于染色体分离至关重要，同时也产生了遗传多样性。减数分裂过程中同源染色体之间的遗传交换是由重组酶 Dmc1 介导的，它能够与有差异的 DNA 序列进行重组。Hop2-Mnd1 复合物介导 Dmc1 的活性。在这里，我们揭示了 Hop2-Mnd1 在限制底物选择方面的调节作用。具体来说，Hop2-Mnd1 上调了与完全同源或含有 DNA 差异的 DNA 底物的 Dmc1 活性，并且它还阻止了仅含有微同源性的底物之间的 DNA 链交换。通过分离和检查突出的 Hop2-Mnd1 功能分离变体，我们表明抑制非法的 DNA 重组需要归因于 Hop2-Mnd1 的 Dmc1 丝的相互作用，而不是其 DNA 结合活性。我们的研究提供了关于 Hop2-Mnd1 如何帮助维持减数分裂重组保真度的机制见解。
