Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process
Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process
复制标题
DOI：
10.1038/ncomms8742
复制
发表时间：
2015-07-01
影响因子：
16.6
通讯作者：
Mekhail, Karim
中科院分区：
文献类型：
--
作者：
Chung, Daniel K. C.;Chan, Janet N. Y.;Mekhail, Karim
DNA双链断裂（DSB）通常靶向核孔复合物（NPC）进行修复。如何实现靶向以及参与这一过程的DNA修复途径仍不清楚。在这里，我们表明，驱动蛋白-14马达蛋白复合物（Cik 1-Kar 3）与染色质重塑介导的亚端粒DSB和NUP 84核孔复合物之间的相互作用，以确保通过断裂诱导的复制（BIR），一个容易出错的DNA修复过程中的细胞存活。在亚端粒DSB位点附近插入一个DNA邮政编码，人为地将其靶向过度激活这种修复机制的NPC。驱动蛋白-14和Nup 84介导非端粒DSB的BIR依赖性修复，而核周端粒栓系仅为端粒BIR所需。此外，驱动蛋白-14在非端粒酶依赖性端粒维持中起关键作用。因此，我们揭示了驱动蛋白和NPC在BIR DNA修复中的作用，并揭示了核周端粒锚许可亚端粒DSB用于这种易错的DNA修复机制。
DNA double-strand breaks (DSBs) are often targeted to nuclear pore complexes (NPCs) for repair. How targeting is achieved and the DNA repair pathways involved in this process remain unclear. Here, we show that the kinesin-14 motor protein complex (Cik1-Kar3) cooperates with chromatin remodellers to mediate interactions between subtelomeric DSBs and the Nup84 nuclear pore complex to ensure cell survival via break-induced replication (BIR), an error-prone DNA repair process. Insertion of a DNA zip code near the subtelomeric DSB site artificially targets it to NPCs hyperactivating this repair mechanism. Kinesin-14 and Nup84 mediate BIR-dependent repair at non-telomeric DSBs whereas perinuclear telomere tethers are only required for telomeric BIR. Furthermore, kinesin-14 plays a critical role in telomerase-independent telomere maintenance. Thus, we uncover roles for kinesin and NPCs in DNA repair by BIR and reveal that perinuclear telomere anchors license subtelomeric DSBs for this error-prone DNA repair mechanism.