Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing.

ABSTRACT: During lagging strand synthesis, DNA Ligase 1 (Lig1) cooperates with the sliding clamp PCNA to seal the nicks between Okazaki fragments generated by Pol δ and Flap endonuclease 1 (FEN1). We present several cryo-EM structures combined with functional assays, showing that human Lig1 recruits PCNA to nicked DNA using two PCNA-interacting motifs (PIPs) located at its disordered N-terminus (PIP_N-term) and DNA binding domain (PIP_DBD). Once Lig1 and PCNA assemble as two-stack rings encircling DNA, PIP_N-term is released from PCNA and only PIP_DBD is required for ligation to facilitate the substrate handoff from FEN1. Consistently, we observed that PCNA forms a defined complex with FEN1 and nicked DNA, and it recruits Lig1 to an unoccupied monomer creating

SUBMITTER: Blair K 

PROVIDER: S-EPMC9767926 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature