Formation of interference-sensitive meiotic cross-overs requires sufficient DNA leading-strand elongation
Formation of interference-sensitive meiotic cross-overs requires sufficient DNA leading-strand elongation
复制标题
对干扰敏感的减数分裂交换的形成需要足够的 DNA 前导链延伸
DOI：
10.1073/pnas.1507165112
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发表时间：
2015-10-06
影响因子：
11.1
通讯作者：
Wang, Yingxiang
中科院分区：
文献类型：
--
作者：
Huang, Jiyue;Cheng, Zhihao;Wang, Yingxiang
意义 减数分裂对于真核有性生殖至关重要，减数分裂重组可在后代中重新分配遗传变异。同源重组对于 DNA 修复和基因组稳定性也很重要。目前的重组模型包括DNA合成，特别是前导链合成，但其作用尚未经过实验测试。在这里，我们发现，前导链延伸所需的 DNA 聚合酶突变会导致生育力下降、减数分裂染色体断裂和分离缺陷以及干扰敏感交换 (CO) 减少。由于大多数减数分裂 CO 是由芽殖酵母、哺乳动物和开花植物中的干扰敏感途径产生的，因此减数分裂重组途径分化中前导链伸长的发现对于理解人类生殖健康和作物育种具有重要意义。减数分裂将二倍体基因组减半为单倍体，对于真核生物的有性繁殖至关重要。减数分裂重组确保同源物的物理关联及其随后的准确分离，并导致后代中遗传变异的重新分配。大多数生物体都有两类交叉 (CO)：干扰敏感（I 型）和干扰不敏感（II 型）CO。 DNA 合成对于减数分裂重组至关重要，但 DNA 合成是否在分化减数分裂 CO 途径中发挥作用尚不清楚。在这里，我们证明拟南芥 POL2A（酵母 DNA 聚合酶-ε（一种前导链 DNA 聚合酶）的同源物）是植物育性和减数分裂所必需的。 POL2A 突变会导致生育力下降和减数分裂缺陷，包括染色体关联异常、染色体分离不当和断裂。对前期 I 细胞分布的观察表明 pol2a 突变体可能延迟减数分裂重组的进展。此外，pol2a中残留的COs减少了CO干扰，并且影响II型COs的pol2a与mus81的双突变体比任一单突变体表现出更严重的缺陷，表明POL2A在I型途径中发挥作用。我们假设足够的前导链 DNA 延伸促进某些 I 型 CO 的形成。鉴于减数分裂重组和 DNA 合成在不同的真核生物中是保守的，这项研究和我们之前的研究表明 DNA 合成在减数分裂重组途径的分化中具有新的作用。
Significance Meiosis is essential for eukaryotic sexual reproduction, and meiotic recombination redistributes genetic variations among progeny. Homologous recombination is also important for DNA repair and genome stability. Current recombination models include DNA synthesis, particularly leading-strand synthesis, but its role has not been tested experimentally. Here, we showed that mutations in a DNA polymerase required for leading-strand elongation caused reduced fertility, defects in meiotic chromosome fragmentation and segregation, and reduction of interference-sensitive cross-overs (COs). Because the majority of meiotic COs are produced from the interference-sensitive pathway in budding yeast, mammals, and flowering plants, the discovery of leading-strand elongation in the differentiation of meiotic recombination pathways has important implications in understanding of human reproductive health and crop breeding. Meiosis halves diploid genomes to haploid and is essential for sexual reproduction in eukaryotes. Meiotic recombination ensures physical association of homologs and their subsequent accurate segregation and results in the redistribution of genetic variations among progeny. Most organisms have two classes of cross-overs (COs): interference-sensitive (type I) and -insensitive (type II) COs. DNA synthesis is essential for meiotic recombination, but whether DNA synthesis has a role in differentiating meiotic CO pathways is unknown. Here, we show that Arabidopsis POL2A, the homolog of the yeast DNA polymerase-ε (a leading-strand DNA polymerase), is required for plant fertility and meiosis. Mutations in POL2A cause reduced fertility and meiotic defects, including abnormal chromosome association, improper chromosome segregation, and fragmentation. Observation of prophase I cell distribution suggests that pol2a mutants likely delay progression of meiotic recombination. In addition, the residual COs in pol2a have reduced CO interference, and the double mutant of pol2a with mus81, which affects type II COs, displayed more severe defects than either single mutant, indicating that POL2A functions in the type I pathway. We hypothesize that sufficient leading-strand DNA elongation promotes formation of some type I COs. Given that meiotic recombination and DNA synthesis are conserved in divergent eukaryotes, this study and our previous study suggest a novel role for DNA synthesis in the differentiation of meiotic recombination pathways.