7QNZ
human Lig1-DNA-PCNA complex reconstituted in absence of ATP
Summary for 7QNZ
Entry DOI | 10.2210/pdb7qnz/pdb |
EMDB information | 14078 |
Descriptor | DNA ligase 1, Proliferating cell nuclear antigen, Oligo19ddC, ... (6 entities in total) |
Functional Keywords | dna, replication, complex, ligase, pcna, ligation, okazaki fragment maturation |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 7 |
Total formula weight | 209113.19 |
Authors | Blair, K.,Tehseen, M.,Raducanu, V.S.,Shahid, T.,Lancey, C.,Cruehet, R.,Hamdan, S.,De Biasio, A. (deposition date: 2021-12-23, release date: 2023-01-11, Last modification date: 2024-07-17) |
Primary citation | Blair, K.,Tehseen, M.,Raducanu, V.S.,Shahid, T.,Lancey, C.,Rashid, F.,Creuhet, R.,Hamdan, S.M.,De Biasio, A. Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing. Nat Commun, 13:7833-7833, 2022 Cited by PubMed 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) and DNA binding domain (PIP). Once Lig1 and PCNA assemble as two-stack rings encircling DNA, PIP is released from PCNA and only PIP 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. PubMed: 36539424DOI: 10.1038/s41467-022-35475-z PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (4.58 Å) |
Structure validation
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