A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.

ABSTRACT: During replication, lagging strand lesions are initially encountered by high-fidelity DNA polymerase (pol) holoenzymes comprised of pol δ and the PCNA sliding clamp. To proceed unhindered, pol δ holoenzymes must bypass lesions without stalling. This entails dNMP incorporation opposite the lesion (insertion) and the 5' template deoxynucleotide (extension). Historically, it was viewed that high-fidelity pol holoenzymes stall upon encountering lesions, activating DNA damage tolerance pathways that are ultimately responsible for lesion bypass. Our recent study of four prominent lesions revealed that human pol δ holoenzymes support insertion and/or bypass for multiple lesions and the extent of these activities depends on the lesion and pol δ proofreading. In the present study, we expand these a

SUBMITTER: Dannenberg RL 

PROVIDER: S-EPMC12266135 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature