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Publication Abstract from PubMed

During lagging strand synthesis, DNA Ligase 1 (Lig1) cooperates with the sliding clamp PCNA to seal the nicks between Okazaki fragments generated by Pol delta 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 a toolbelt that drives the transfer of DNA to Lig1. Collectively, our results provide a structural model on how PCNA regulates FEN1 and Lig1 during Okazaki fragments maturation.

Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing.,Blair K, Tehseen M, Raducanu VS, Shahid T, Lancey C, Rashid F, Crehuet R, Hamdan SM, De Biasio A Nat Commun. 2022 Dec 20;13(1):7833. doi: 10.1038/s41467-022-35475-z. PMID:36539424^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.