WRNIP1 (WRN-interacting protein 1) was first identified as a factor that interacts with WRN, the protein that is defective in Werner syndrome (WS). WRNIP1 associates with DNA polymerase eta (Pol eta), but the biological significance of this interaction remains unknown. In this study, we analyzed the functional interaction between WRNIP1 and Pol eta by generating knockouts of both genes in DT40 chicken cells. Disruption of WRNIP1 in Pol eta-disrupted (POLH-/-) cells suppressed the phenotypes associated with the loss of Pol eta: sensitivity to ultraviolet light (UV), delayed repair of cyclobutane pyrimidine dimers (CPD), elevated frequency of mutation, elevated levels of UV-induced sister chromatid exchange (SCE), and reduced rate of fork progression after UV irradiation. These results suggest that WRNIP1 functions upstream of Pol eta in the response to UV irradiation. (C) 2014 Elsevier Inc. All rights reserved.