Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, 3327-204, Nakamachi, Nara, 631-8505, Japan.
Biochem Biophys Res Commun. 2018 Jul 2;501(4):1080-1084. doi: 10.1016/j.bbrc.2018.05.111. Epub 2018 May 21.
A DNA double strand break (DSB) is one of the most cytotoxic DNA lesions, but it can be repaired by non-homologous end joining (NHEJ) or by homologous recombination. The choice between these two repair pathways depends on the cell cycle stage. Although NHEJ constitutes a simple re-ligation reaction, the regulatory mechanism(s) controlling its activity has not been fully characterized. Lif1 is a regulatory subunit of the NHEJ-specific DNA ligase IV and interacts with Xrs2 of the MRX complex which is a key factor in DSB repair. Specifically, the C-terminal region of Lif1, which contains a CK2-specific phosphorylation motif, interacts with the FHA domain of Xrs2 during canonical- NHEJ (C-NHEJ). Herein, we show that Lif1 and Cka2, a catalytic subunit of yeast CK2, interact and that the C-terminal phosphorylation consensus motif in Lif1 is phosphorylated by recombinant CK2. These observations suggest that phosphorylation of Lif1 by CK2 at a DSB site promotes the Lif1-Xrs2 interaction and facilitates C-NHEJ.
DNA 双链断裂 (DSB) 是最具细胞毒性的 DNA 损伤之一，但它可以通过非同源末端连接 (NHEJ) 或同源重组来修复。这两种修复途径的选择取决于细胞周期阶段。尽管 NHEJ 构成了一个简单的重新连接反应，但控制其活性的调节机制尚未完全表征。Lif1 是 NHEJ 特异性 DNA 连接酶 IV 的调节亚基，与 MRX 复合物的 Xrs2 相互作用，MRX 复合物是 DSB 修复的关键因素。具体来说，Lif1 的 C 端区域包含一个 CK2 特异性磷酸化模体，在规范的 NHEJ (C-NHEJ) 期间与 Xrs2 的 FHA 结构域相互作用。在此，我们表明 Lif1 和 Cka2（酵母 CK2 的催化亚基）相互作用，并且 Lif1 中的 C 端磷酸化共有序列基序被重组 CK2 磷酸化。这些观察结果表明，CK2 在 DSB 位点对 Lif1 的磷酸化促进了 Lif1-Xrs2 相互作用，并促进了 C-NHEJ。
