Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.
Department of Basic Medical Sciences, St Georges, University of London, London, UK.
Genes Cells. 2021 Apr;26(4):219-229. doi: 10.1111/gtc.12836. Epub 2021 Mar 18.
In eukaryotes, specific DNA-protein structures called telomeres exist at linear chromosome ends. Telomere stability is maintained by a specific capping protein complex. This capping complex is essential for the inhibition of the DNA damage response (DDR) at telomeres and contributes to genome integrity. In Drosophila, the central factors of telomere capping complex are HOAP and HipHop. Furthermore, a DDR protein complex Mre11-Rad50-Nbs (MRN) is known to be important for the telomere association of HOAP and HipHop. However, whether MRN interacts with HOAP and HipHop, and the telomere recognition mechanisms of HOAP and HipHop are poorly understood. Here, we show that Nbs interacts with Mre11 and transports the Mre11-Rad50 complex from the cytoplasm to the nucleus. In addition, we report that HOAP interacts with both Mre11 and Nbs. The N-terminal region of HOAP is essential for its co-localization with HipHop. Finally, we reveal that Nbs interacts with the N-terminal region of HOAP.
在真核生物中，线性染色体末端存在称为端粒的特定 DNA-蛋白质结构。端粒稳定性由特定的盖帽蛋白复合物维持。该盖帽复合物对于抑制端粒处的 DNA 损伤反应 (DDR) 至关重要，并有助于基因组完整性。在果蝇中，端粒盖帽复合物的核心因子是 HOAP 和 HipHop。此外，众所周知，DDR 蛋白复合物 Mre11-Rad50-Nbs (MRN) 对于 HOAP 和 HipHop 与端粒的关联很重要。然而，MRN 是否与 HOAP 和 HipHop 相互作用，以及 HOAP 和 HipHop 的端粒识别机制尚不清楚。在这里，我们表明 Nbs 与 Mre11 相互作用，并将 Mre11-Rad50 复合物从细胞质运输到细胞核。此外，我们报告 HOAP 与 Mre11 和 Nbs 都相互作用。HOAP 的 N 端区域对于其与 HipHop 的共定位是必不可少的。最后，我们揭示了 Nbs 与 HOAP 的 N 端区域相互作用。
