Abstrakt

A function checkpoint kinase with catalytical independence exists in human DNA.

Miriam Merad

The specific DNA synthesis activity of DNA polymerase kappa (Pol k) during translesion replication, progression of replication forks through challenging replication regions, restart of stalled forks, and replication checkpoint effectiveness have all received considerable attention to date. Pol k is also necessary for the stabilisation of forks that have stalled, though the mechanisms are unclear. In this study, we discovered an unexpected function for Pol k in regulating checkpoint kinase 1 (Chk1), a crucial player in replication checkpoint. In the nuclei of four human cell lines, we discovered that the loss of Pol k reduced the level of the Chk1 protein. To maintain the Chk1 protein pool throughout the cell cycle, Pol k-and not the other Y family polymerase members-is necessary. We demonstrated how Pol k depletion impacted Chk1's protein stability and guarded it against proteasome degradation. Importantly, we also discovered that the repressions of Chk1 could compensate for the fork restart defects seen in Pol k-depleted cells. Surprisingly, this new role for Pol k does not depend on its catalytic activity. We suggest that Chk1 stability caused by Pol k may help to protect stalled forks.