Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Mol Cell. 2021 Oct 21;81(20):4258-4270.e4. doi: 10.1016/j.molcel.2021.08.003. Epub 2021 Aug 27.
Currently favored models for meiotic recombination posit that both noncrossover and crossover recombination are initiated by DNA double-strand breaks but form by different mechanisms: noncrossovers by synthesis-dependent strand annealing and crossovers by formation and resolution of double Holliday junctions centered around the break. This dual mechanism hypothesis predicts different hybrid DNA patterns in noncrossover and crossover recombinants. We show that these predictions are not upheld, by mapping with unprecedented resolution parental strand contributions to recombinants at a model locus. Instead, break repair in both noncrossovers and crossovers involves synthesis-dependent strand annealing, often with multiple rounds of strand invasion. Crossover-specific double Holliday junction formation occurs via processes involving branch migration as an integral feature, one that can be separated from repair of the break itself. These findings reveal meiotic recombination to be a highly dynamic process and prompt a new view of the relationship between crossover and noncrossover recombination.
目前,关于减数分裂重组的主流模型假设,非交叉重组和交叉重组都是由 DNA 双链断裂引发的,但形成的机制不同:非交叉重组通过合成依赖性链退火形成,而交叉重组则通过形成和解析以断裂为中心的双链 Holliday 连接体形成。这种双重机制假说预测了非交叉重组和交叉重组体中不同的杂种 DNA 模式。我们通过在一个模型基因座上以空前的分辨率绘制重组体中亲本链的贡献,表明这些预测并不成立。相反,非交叉重组和交叉重组中的断裂修复都涉及合成依赖性链退火,通常涉及多次链入侵。交叉重组特有的双链 Holliday 连接体形成是通过分支迁移作为一个整体特征的过程发生的,分支迁移可以与断裂本身的修复过程分离。这些发现揭示了减数分裂重组是一个高度动态的过程,并促使人们对交叉重组和非交叉重组之间的关系产生了新的认识。