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-Structure paper
タイトル | Structure of the processive human Pol δ holoenzyme. |
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ジャーナル・号・ページ | Nat Commun, Vol. 11, Issue 1, Page 1109, Year 2020 |
掲載日 | 2020年2月28日 |
著者 | Claudia Lancey / Muhammad Tehseen / Vlad-Stefan Raducanu / Fahad Rashid / Nekane Merino / Timothy J Ragan / Christos G Savva / Manal S Zaher / Afnan Shirbini / Francisco J Blanco / Samir M Hamdan / Alfredo De Biasio / |
PubMed 要旨 | In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki ...In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ-DNA-PCNA complex in the absence and presence of FEN1. Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol δ's activity in replicating the human genome. |
リンク | Nat Commun / PubMed:32111820 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.08 - 8.1 Å |
構造データ | EMDB-10080, PDB-6s1m: EMDB-10081, PDB-6s1n: EMDB-10082, PDB-6s1o: EMDB-10539, PDB-6tny: EMDB-10540, PDB-6tnz: |
化合物 | ChemComp-ZN: ChemComp-SF4: ChemComp-TTP: |
由来 |
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キーワード | REPLICATION / Protein |