Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11370-5. doi: 10.1073/pnas.1004248107. Epub 2010 Jun 3.
Meiosis generates four haploid daughters from a diploid parental cell. Central steps of meiosis are the pairing and recombination of homologous chromosomes followed by their segregation in two rounds of cell division. Meiotic recombination is monitored by a specialized DNA damage checkpoint pathway and is guided by a unique chromosomal structure called synaptonemal complex (SC), but how these events are coordinated is unclear. Here, we identify the SC protein Red1 as a crucial regulator of early meiosis. Red1 interacts with two subunits of the 9-1-1 checkpoint complex via two distinct 9-1-1 subunit-specific motifs. Association of 9-1-1 with Red1 is essential not only for meiotic checkpoint activation but for SC formation. Moreover, Red1 becomes SUMO-modified, which fosters interaction of Red1 with the central SC element Zip1, thereby securing timely SC formation. Thus, Red1, in addition to its structural role in the SC, is a crucial coordinator of meiosis by coupling checkpoint signaling to SC formation.
减数分裂从二倍体亲本细胞产生四个单倍体的女儿细胞。减数分裂的中心步骤是同源染色体的配对和重组,随后在两轮细胞分裂中进行分离。减数分裂重组由专门的 DNA 损伤检查点途径监测,并由称为联会复合体 (SC) 的独特染色体结构指导,但这些事件如何协调尚不清楚。在这里,我们确定 SC 蛋白 Red1 是早期减数分裂的关键调节因子。Red1 通过两个独特的 9-1-1 亚基特异性基序与 9-1-1 检查点复合物的两个亚基相互作用。9-1-1 与 Red1 的结合对于减数分裂检查点的激活以及 SC 的形成都是必不可少的。此外,Red1 被 SUMO 修饰,这促进了 Red1 与中央 SC 元件 Zip1 的相互作用,从而确保了 SC 的及时形成。因此,Red1 除了在 SC 中具有结构作用外,还是通过将检查点信号与 SC 形成偶联来协调减数分裂的关键调节因子。