Department of Chromosome Biology, Max Perutz Labs, University of Vienna, Vienna BioCenter, Vienna, Austria.
Center for Integrative Bioinformatics Vienna (CIBIV), Max Perutz Labs, University of Vienna and Medical University of Vienna, Vienna BioCenter, Vienna, Austria.
Plant Cell. 2021 Jul 2;33(5):1633-1656. doi: 10.1093/plcell/koab045.
Meiosis is a specialized cell division that gives rise to genetically distinct gametic cells. Meiosis relies on the tightly controlled formation of DNA double-strand breaks (DSBs) and their repair via homologous recombination for correct chromosome segregation. Like all forms of DNA damage, meiotic DSBs are potentially harmful and their formation activates an elaborate response to inhibit excessive DNA break formation and ensure successful repair. Previous studies established the protein kinase ATM as a DSB sensor and meiotic regulator in several organisms. Here we show that Arabidopsis ATM acts at multiple steps during DSB formation and processing, as well as crossover (CO) formation and synaptonemal complex (SC) organization, all vital for the successful completion of meiosis. We developed a single-molecule approach to quantify meiotic breaks and determined that ATM is essential to limit the number of meiotic DSBs. Local and genome-wide recombination screens showed that ATM restricts the number of interference-insensitive COs, while super-resolution STED nanoscopy of meiotic chromosomes revealed that the kinase affects chromatin loop size and SC length and width. Our study extends our understanding of how ATM functions during plant meiosis and establishes it as an integral factor of the meiotic program.
减数分裂是一种特殊的细胞分裂,产生遗传上不同的配子细胞。减数分裂依赖于 DNA 双链断裂(DSB)的紧密控制形成及其通过同源重组进行的正确染色体分离修复。与所有形式的 DNA 损伤一样,减数分裂 DSB 具有潜在的危害性,其形成激活了一个复杂的反应,以抑制过多的 DNA 断裂形成并确保成功修复。先前的研究在几种生物中确立了蛋白激酶 ATM 作为 DSB 传感器和减数分裂调节剂的作用。在这里,我们表明拟南芥 ATM 在 DSB 形成和加工、交叉(CO)形成和联会复合体(SC)组织的多个步骤中发挥作用,这些步骤对于减数分裂的成功完成都是至关重要的。我们开发了一种单分子方法来定量减数分裂断裂,并确定 ATM 对于限制减数分裂 DSB 的数量是必不可少的。局部和全基因组重组筛选表明,ATM 限制了不干涉 CO 的数量,而减数分裂染色体的超分辨率 STED 纳米显微镜观察表明,该激酶影响染色质环大小和 SC 的长度和宽度。我们的研究扩展了我们对 ATM 在植物减数分裂过程中的功能的理解,并确立了它作为减数分裂程序的一个组成部分。