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bioRxiv · 10.1101/2021.02.09.430494

A catalytic-independent function of human DNA polymerase Kappa controls the pool of the Checkpoint Kinase 1

Dall'Osto, M.·Pierini, L.·Valery, N.·Hoffmann, J.-S.·Pillaire, M.-J.
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Abstract

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 and replication checkpoint at stalled forks. Here we unveiled an unexpected role for Pol {kappa} in controlling the stability and abundance of Chk1, the major mediator of the replication checkpoint. We found that loss of Pol {kappa} decreased the Chk1 protein level in the nucleus 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 and the replication recovery defects observed in Pol {kappa}-depleted cells could be overcome by the re-expression of Chk1. Importantly, this new function of Pol {kappa} does not require its catalytic activity, revealing that in addition to its known roles in the replication process, Pol {kappa} can contribute to the maintenance of genome stability independently of its DNA synthesis activity.

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Dall'Osto, M., Pierini, L., Valery, N., Hoffmann, J.-S., Pillaire, M.-J.. 2021-02-09. A catalytic-independent function of human DNA polymerase Kappa controls the pool of the Checkpoint Kinase 1. https://doi.org/10.1101/2021.02.09.430494

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