Wang Guishuan, Wu Xiaolong, Zhou Liwei, Gao Sheng, Yun Damin, Liang Ajuan, Sun Fei
Medical School, Institute of Reproductive Medicine, Nantong University, Nantong, China.
Reproductive Medical Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Front Cell Dev Biol. 2020 Sep 4;8:845. doi: 10.3389/fcell.2020.00845. eCollection 2020.
During meiosis, telomeres attach to the nuclear envelope (NE) to promote homologous chromosome moving, pairing, synapsis, and recombination. The telomere-NE attachment is mediated by SUN1, TERB1-TERB2-MAJIN (TTM complex), and TRF1. The interaction of the TTM complex with shelterin is mediated by TERB1 and TRF1, but how SUN1 interacts with the TTM complex is not yet fully understood. In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. The binding sites of MAJIN and SPDYA at SUN1 were mapped, and both MAJIN and SPDYA bound to the N-terminal domain of SUN1 and the two binding sites were close to each other. Furthermore, SPDYA bound to SUN1 via the Ringo domain and recruited CDK2 to SUN1. Then, we found that the interaction of SUN1 with MAJIN was decreased by the CDK2 inhibitors. Taken together, our results provide the possible mechanism of SUN1, MAJIN, and SPDYA-CDK2 in promoting the telomere-NE attachment during meiosis.
在减数分裂过程中，端粒附着于核膜（NE）以促进同源染色体移动、配对、联会和重组。端粒与核膜的附着由SUN1、TERB1-TERB2-MAJIN（TTM复合体）和TRF1介导。TTM复合体与端粒保护蛋白的相互作用由TERB1和TRF1介导，但SUN1如何与TTM复合体相互作用尚未完全了解。在本研究中，我们发现SUN1不仅与TERB1相互作用，还与MAJIN相互作用，且SUN1与MAJIN的相互作用强于与TERB1的相互作用。我们还发现SUN1与细胞周期蛋白依赖性激酶2（CDK2）的激活剂SPDYA相互作用。确定了MAJIN和SPDYA在SUN1上的结合位点，MAJIN和SPDYA均与SUN1的N端结构域结合，且两个结合位点彼此靠近。此外，SPDYA通过Ringo结构域与SUN1结合并将CDK2招募至SUN1。然后，我们发现CDK2抑制剂可降低SUN1与MAJIN的相互作用。综上所述，我们的结果揭示了SUN1、MAJIN以及SPDYA-CDK2在减数分裂过程中促进端粒与核膜附着的可能机制。
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