| Structural highlights
Function
DPOD3_HUMAN Required for optimal DNA polymerase delta activity.[1] [2] [3]
Publication Abstract from PubMed
In eukaryotes, DNA polymerase delta (Pol delta) 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 delta-DNA-PCNA complex in the absence and presence of FEN1. Pol delta 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 delta's activity in replicating the human genome.
Structure of the processive human Pol delta holoenzyme.,Lancey C, Tehseen M, Raducanu VS, Rashid F, Merino N, Ragan TJ, Savva CG, Zaher MS, Shirbini A, Blanco FJ, Hamdan SM, De Biasio A Nat Commun. 2020 Feb 28;11(1):1109. doi: 10.1038/s41467-020-14898-6. PMID:32111820[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hughes P, Tratner I, Ducoux M, Piard K, Baldacci G. Isolation and identification of the third subunit of mammalian DNA polymerase delta by PCNA-affinity chromatography of mouse FM3A cell extracts. Nucleic Acids Res. 1999 May 15;27(10):2108-14. PMID:10219083
- ↑ Mo J, Liu L, Leon A, Mazloum N, Lee MY. Evidence that DNA polymerase delta isolated by immunoaffinity chromatography exhibits high-molecular weight characteristics and is associated with the KIAA0039 protein and RPA. Biochemistry. 2000 Jun 20;39(24):7245-54. PMID:10852724
- ↑ Li H, Xie B, Zhou Y, Rahmeh A, Trusa S, Zhang S, Gao Y, Lee EY, Lee MY. Functional roles of p12, the fourth subunit of human DNA polymerase delta. J Biol Chem. 2006 May 26;281(21):14748-55. Epub 2006 Feb 28. PMID:16510448 doi:http://dx.doi.org/10.1074/jbc.M600322200
- ↑ Lancey C, Tehseen M, Raducanu VS, Rashid F, Merino N, Ragan TJ, Savva CG, Zaher MS, Shirbini A, Blanco FJ, Hamdan SM, De Biasio A. Structure of the processive human Pol delta holoenzyme. Nat Commun. 2020 Feb 28;11(1):1109. doi: 10.1038/s41467-020-14898-6. PMID:32111820 doi:http://dx.doi.org/10.1038/s41467-020-14898-6
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