Kumar Rajeev, Ghyselinck Norbert, Ishiguro Kei-ichiro, Watanabe Yoshinori, Kouznetsova Anna, Höög Christer, Strong Edward, Schimenti John, Daniel Katrin, Toth Attila, de Massy Bernard
Institute of Human Genetics, UPR 1142, CNRS. 141, Rue de la Cardonille, 34396 Montpellier, France.
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104 - INSERM U964, Department of Functional Genomics and Cancer, 1 rue Laurent Fries, BP10142, 67404 ILLKIRCH CEDEX, France.
J Cell Sci. 2015 May 1;128(9):1800-11. doi: 10.1242/jcs.165464. Epub 2015 Mar 20.
The formation of programmed DNA double-strand breaks (DSBs) at the beginning of meiotic prophase marks the initiation of meiotic recombination. Meiotic DSB formation is catalyzed by SPO11 and their repair takes place on meiotic chromosome axes. The evolutionarily conserved MEI4 protein is required for meiotic DSB formation and is localized on chromosome axes. Here, we show that HORMAD1, one of the meiotic chromosome axis components, is required for MEI4 localization. Importantly, the quantitative correlation between the level of axis-associated MEI4 and DSB formation suggests that axis-associated MEI4 could be a limiting factor for DSB formation. We also show that MEI1, REC8 and RAD21L are important for proper MEI4 localization. These findings on MEI4 dynamics during meiotic prophase suggest that the association of MEI4 to chromosome axes is required for DSB formation, and that the loss of this association upon DSB repair could contribute to turning off meiotic DSB formation.
减数分裂前期开始时程序性DNA双链断裂（DSB）的形成标志着减数分裂重组的启动。减数分裂DSB的形成由SPO11催化，其修复发生在减数分裂染色体轴上。进化上保守的MEI4蛋白是减数分裂DSB形成所必需的，并且定位于染色体轴上。在这里，我们表明减数分裂染色体轴成分之一的HORMAD1是MEI4定位所必需的。重要的是，与轴相关的MEI4水平与DSB形成之间的定量相关性表明，与轴相关的MEI4可能是DSB形成的限制因素。我们还表明MEI1、REC8和RAD21L对MEI4的正确定位很重要。这些关于减数分裂前期MEI4动态变化的发现表明，MEI4与染色体轴的结合是DSB形成所必需的，并且DSB修复时这种结合的丧失可能有助于关闭减数分裂DSB的形成。
