Erschienen:
Proceedings of the National Academy of Sciences, 2016
Erschienen in:
Proceedings of the National Academy of Sciences, 113 (2016) 30
Sprache:
Englisch
DOI:
10.1073/pnas.1605828113
ISSN:
0027-8424;
1091-6490
Entstehung:
Anmerkungen:
Beschreibung:
SignificanceDNA damage tolerance pathways like translesion synthesis and recombination facilitate the bypass of replication-blocking lesions. Such events are crucial for the survival of rapidly proliferating cells, including cancer and stem cells undergoing active duplication during tissue renewal. Herein, we characterize an unprecedented damage tolerance pathway that requires the combined function of a highly enigmatic translesion DNA polymerase ι (POLι) and the so-called guardian-of-the-genome, p53. We provide evidence demonstrating that p53 complexed with POLι triggers idling events that decelerate nascent DNA elongation at replication barriers, facilitating the resolution of stalled forks by specialized structure-specific enzymes. Our findings implicate p53 in the protection of quickly growing cancer and stem cells from endogenous and exogenous sources of replication stress.