Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599.
Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599.
Genetics. 2018 Feb;208(2):579-588. doi: 10.1534/genetics.117.300634. Epub 2017 Dec 15.
Meiotic crossovers must be properly patterned to ensure accurate disjunction of homologous chromosomes during meiosis I. Disruption of the spatial distribution of crossovers can lead to nondisjunction, aneuploidy, gamete dysfunction, miscarriage, or birth defects. One of the earliest identified genes involved in proper crossover patterning is , which encodes the ortholog of the checkpoint kinase ATR. Analysis of hypomorphic mutants suggested the existence of crossover patterning defects, but it was not possible to assess this in null mutants because of maternal-effect embryonic lethality. To overcome this lethality, we constructed null mutants in which we expressed wild-type Mei-41 in the germline after completion of meiotic recombination, allowing progeny to survive. We find that crossovers are decreased to about one-third of wild-type levels, but the reduction is not uniform, being less severe in the proximal regions of chromosome L than in medial or distal L or on the chromosome. None of the crossovers formed in the absence of Mei-41 require Mei-9, the presumptive meiotic resolvase, suggesting that Mei-41 functions everywhere, despite the differential effects on crossover frequency. Interference appears to be significantly reduced or absent in mutants, but the reduction in crossover density in centromere-proximal regions is largely intact. We propose that crossover patterning is achieved in a stepwise manner, with the crossover suppression related to proximity to the centromere occurring prior to and independently of crossover designation and enforcement of interference. In this model, Mei-41 has an essential function in meiotic recombination after the centromere effect is established but before crossover designation and interference occur.
减数分裂交叉必须正确形成模式，以确保减数分裂 I 期间同源染色体的正确分离。交叉空间分布的破坏可导致非分离、非整倍体、配子功能障碍、流产或出生缺陷。最早鉴定出的参与正确交叉模式形成的基因之一是 ，它编码检查点激酶 ATR 的同源物。对功能减弱突变体的分析表明存在交叉模式缺陷，但由于母性效应胚胎致死性，无法在 null 突变体中评估这一点。为了克服这种致死性，我们构建了 null 突变体，在减数分裂重组完成后，野生型 Mei-41 在生殖细胞中表达，使后代能够存活。我们发现交叉减少到大约野生型水平的三分之一，但减少并不均匀，在染色体 L 的近端区域比在中或远端 L 或 染色体上减少得更不严重。在没有 Mei-41 的情况下形成的交叉中，没有一个需要 Mei-9，即假定的减数分裂解旋酶，这表明 Mei-41 无处不在发挥作用，尽管对交叉频率的影响不同。在 突变体中，干扰似乎明显减少或不存在，但着丝粒近端区域的交叉密度减少基本完整。我们提出，交叉模式形成是分阶段进行的，与着丝粒的接近相关的交叉抑制发生在交叉指定和干扰的执行之前和独立于交叉指定和干扰的执行。在这个模型中，Mei-41 在建立着丝粒效应后但在交叉指定和干扰发生之前在减数分裂重组中具有重要功能。
