Defective Repair of G<sub>1</sub>-Phase Double-Strand Breaks in <i>WRNIP1/Ku70</i> Double Knockout Cells

Werner helicase-interacting protein 1 (WRNIP1) is a member of the AAA⁺ ATPase family and is conserved from Escherichia coli to Homo sapiens. Although a role for WRNIP1 in the S phase of the cell cycle has previously been reported, the present study demonstrates a novel function for this protein in G₁ phase. Deletion of WRNIP1 in non-homologous end joining (NHEJ)-deficient chicken DT40 cell lines resulted in slow growth, accumulation in G₁ phase, an increased population of dead cells, and accumulation of double-strand breaks (DSBs), which were indirectly evaluated by γH2AX. The data suggest that WRNIP1 prevents the generation of DSBs, executes DSB repair, and/or regulates DSB repair independently of NHEJ, particularly in G₁ phase. The potential molecular mechanism by which WRNIP1 functions in G₁ phase is discussed.