Daniel Katrin, Tränkner Daniel, Wojtasz Lukasz, Shibuya Hiroki, Watanabe Yoshinori, Alsheimer Manfred, Tóth Attila
Institute of Physiological Chemistry, Technische Universität Dresden, Fiedlerstr, 42, Dresden 01307, Germany.
BMC Cell Biol. 2014 May 22;15:17. doi: 10.1186/1471-2121-15-17.
Telomeres have crucial meiosis-specific roles in the orderly reduction of chromosome numbers and in ensuring the integrity of the genome during meiosis. One such role is the attachment of telomeres to trans-nuclear envelope protein complexes that connect telomeres to motor proteins in the cytoplasm. These trans-nuclear envelope connections between telomeres and cytoplasmic motor proteins permit the active movement of telomeres and chromosomes during the first meiotic prophase. Movements of chromosomes/telomeres facilitate the meiotic recombination process, and allow high fidelity pairing of homologous chromosomes. Pairing of homologous chromosomes is a prerequisite for their correct segregation during the first meiotic division. Although inner-nuclear envelope proteins, such as SUN1 and potentially SUN2, are known to bind and recruit meiotic telomeres, these proteins are not meiosis-specific, therefore cannot solely account for telomere-nuclear envelope attachment and/or for other meiosis-specific characteristics of telomeres in mammals.
We identify CCDC79, alternatively named TERB1, as a meiosis-specific protein that localizes to telomeres from leptotene to diplotene stages of the first meiotic prophase. CCDC79 and SUN1 associate with telomeres almost concurrently at the onset of prophase, indicating a possible role for CCDC79 in telomere-nuclear envelope interactions and/or telomere movements. Consistent with this scenario, CCDC79 is missing from most telomeres that fail to connect to SUN1 protein in spermatocytes lacking the meiosis-specific cohesin SMC1B. SMC1B-deficient spermatocytes display both reduced efficiency in telomere-nuclear envelope attachment and reduced stability of telomeres specifically during meiotic prophase. Importantly, CCDC79 associates with telomeres in SUN1-deficient spermatocytes, which strongly indicates that localization of CCDC79 to telomeres does not require telomere-nuclear envelope attachment.
CCDC79 is a meiosis-specific telomere associated protein. Based on our findings we propose that CCDC79 plays a role in meiosis-specific telomere functions. In particular, we favour the possibility that CCDC79 is involved in telomere-nuclear envelope attachment and/or the stabilization of meiotic telomeres. These conclusions are consistent with the findings of an independently initiated study that analysed CCDC79/TERB1 functions.
端粒在减数分裂过程中染色体数量的有序减少以及确保基因组完整性方面具有关键的减数分裂特异性作用。其中一个作用是端粒与跨核膜蛋白复合物的附着,该复合物将端粒与细胞质中的动力蛋白相连。端粒与细胞质动力蛋白之间的这些跨核膜连接允许在第一次减数分裂前期端粒和染色体的主动移动。染色体/端粒的移动促进减数分裂重组过程,并允许同源染色体进行高保真配对。同源染色体配对是其在第一次减数分裂期间正确分离的前提条件。虽然已知内核膜蛋白,如SUN1以及可能的SUN2,可结合并募集减数分裂端粒,但这些蛋白并非减数分裂特异性的,因此不能单独解释哺乳动物中端粒与核膜的附着和/或端粒的其他减数分裂特异性特征。
我们鉴定出CCDC79(也称为TERB1)是一种减数分裂特异性蛋白,它在第一次减数分裂前期从细线期到双线期定位于端粒。CCDC79和SUN1在前期开始时几乎同时与端粒结合,这表明CCDC79在端粒与核膜相互作用和/或端粒移动中可能发挥作用。与此情况一致的是,在缺乏减数分裂特异性黏连蛋白SMC1B的精母细胞中,大多数未能与SUN1蛋白连接的端粒中不存在CCDC79。缺乏SMC1B的精母细胞在端粒与核膜附着方面效率降低,并且特别是在减数分裂前期端粒稳定性降低。重要的是,CCDC79在缺乏SUN1的精母细胞中与端粒结合,这强烈表明CCDC79定位于端粒不需要端粒与核膜的附着。
CCDC79是一种减数分裂特异性端粒相关蛋白。基于我们的发现,我们提出CCDC79在减数分裂特异性端粒功能中发挥作用。特别是,我们倾向于CCDC79参与端粒与核膜附着和/或减数分裂端粒稳定化的可能性。这些结论与一项独立开展的分析CCDC79/TERB1功能的研究结果一致。