Taiwan International Graduate Program in Molecular and Cellular Biology, Academia Sinica, Taipei 11529, Taiwan.
Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
Proc Natl Acad Sci U S A. 2021 Feb 23;118(8). doi: 10.1073/pnas.2007192118.
Most eukaryotes possess two RecA-like recombinases (ubiquitous Rad51 and meiosis-specific Dmc1) to promote interhomolog recombination during meiosis. However, some eukaryotes have lost Dmc1. Given that mammalian and yeast () Dmc1 have been shown to stabilize recombination intermediates containing mismatches better than Rad51, we used the Pezizomycotina filamentous fungus to address if and how Rad51-only eukaryotes conduct interhomolog recombination in zygotes with high sequence heterogeneity. We applied multidisciplinary approaches (next- and third-generation sequencing technology, genetics, cytology, bioinformatics, biochemistry, and single-molecule biophysics) to show that Rad51 (Rad51) is indispensable for interhomolog recombination during meiosis and, like Dmc1, Rad51 possesses better mismatch tolerance than Rad51 during homologous recombination. Our results also indicate that the ancestral Rad51 evolved to acquire Dmc1-like properties by creating multiple structural variations, including via amino acid residues in the L1 and L2 DNA-binding loops.
大多数真核生物拥有两种 RecA 样重组酶（普遍存在的 Rad51 和减数分裂特异性的 Dmc1），以促进减数分裂过程中同源重组。然而，一些真核生物已经失去了 Dmc1。鉴于哺乳动物和酵母 () Dmc1 已被证明比 Rad51 更能稳定含有错配的重组中间体，我们利用子囊菌门丝状真菌 来研究仅有 Rad51 的真核生物是否以及如何在具有高度序列异质性的受精卵中进行同源重组。我们采用了多学科方法（下一代和第三代测序技术、遗传学、细胞学、生物信息学、生物化学和单分子生物物理学）来表明 Rad51（Rad51）在减数分裂过程中同源重组是必不可少的，并且与 Dmc1 一样，Rad51 在同源重组过程中具有比 Rad51 更好的错配容忍度。我们的结果还表明，祖先 Rad51 通过创建多个结构变异（包括 L1 和 L2 DNA 结合环中的氨基酸残基），进化为获得 Dmc1 样特性。
