Defective Repair of G1-Phase Double-Strand Breaks in WRNIP1/Ku70 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.