E3 ubiquitin ligase RNF2 protects polymerase t from destabilization

Human DNA polymerase t (Polt) belongs to the Y -family of specialized DNA polymerases engaged in the DNA damage tolerance pathway of translesion DNA synthesis that is crucial to the maintenance of genome integrity. The extreme infidelity of Polt and the fact that both its up- and down -regulation correlate with various cancers indicate that Polt expression and access to the replication fork should be strictly controlled. Here, we identify RNF2, an E3 ubiquitin ligase, as a new interacting partner of Polt that is responsible for Polt stabilization in vivo . Interestingly, while we report that RNF2 does not directly ubiquitinate Polt, inhibition of the E3 ubiquitin ligase activity of RNF2 affects the cellular level of Polt thereby protecting it from destabilization. Additionally, we indicate that this mechanism is more general, as DNA polymerase eta, another Y -family polymerase and the closest paralogue of Polt, share similar features.