A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1

DNA polymerase kappa (Pol kappa) has been well documented thus far for its specialized DNA synthesis activity during translesion replication, progression of replication forks through regions difficult to replicate, restart of stalled forks, and replication checkpoint efficiency. Pol kappa is also required for the stabilization of stalled forks, although the mechanisms are poorly understood. In this study, we unveiled an unexpected role for Pol kappa in controlling the stability and abundance of checkpoint kinase 1 (Chk1), an important actor for the replication checkpoint and fork stabilization. We found that loss of Pol kappa decreased the Chk1 protein level in the nuclei of four human cell lines. Pol kappa and not the other Y family polymerase members is required to maintain the Chk1 protein pool all along the cell cycle. We showed that Pol kappa depletion affected the protein stability of Chk1 and protected it from proteasome degradation. Importantly, we also observed that the fork restart defects observed in Pol kappa-depleted cells could be overcome by the reexpression of Chk1. Strikingly, this new function of Pol kappa does not require its catalytic activity. We propose that Pol kappa could contribute to the protection of stalled forks through Chk1 stability.