An Article "DNA damage tolerance pathway involving DNA polymerase ι and the tumor suppressor p53
regulates DNA replication fork progression" in PNAS published by Helmut Pospiech and his multinational collaborators
DNA damage tolerance facilitates the progression of replication forks that have encountered obstacles on the template strands. It involves either translesion DNA synthesis, fork reversal or template switch mechanisms. We characterize a novel tolerance pathway requiring the tumor suppressor p53 in addition to previously recognised DNA damage tolerance factor such as the translesion polymerase ι (POLι). This novel p53 activity is lost in the exonuclease-deficient but transcriptionally active p53(H115N) mutant. p53 associates with POLι to decelerate nascent DNA elongation and promote HLTF/ZRANB3-dependent recombination during unperturbed DNA replication. These results implicate a direct role of p53 in the processing of replication forks encountering obstacles on the template strand.
Viimeksi päivitetty: 24.8.2016