Casein kinase II phosphorylates the C-terminal region of Lif1 to promote the Lif1-Xrs2 interaction needed for non-homologous end joining

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 Lift is phosphorylated by recombinant CK2. These observations suggest that phosphorylation of Lift by CK2 at a DSB site promotes the Lif1-Xrs2 interaction and facilitates C-NHEJ. (C) 2018 The Authors. Published by Elsevier Inc.