6v8p
From Proteopedia
Structure of DNA Polymerase Zeta (Apo)
Structural highlights
FunctionDPOZ_YEAST Nonessential DNA polymerase. Required for DNA damage induced mutagenesis. Involved in DNA repair, mitochondrial DNA repair and translesion synthesis. Translesion synthesis in S.cerevisiae may use a specialized DNA polymerase that is not required for other DNA replicative processes. Has a role in the bypass of abasic (AP) sites. Highly inefficient in incorporating nucleotides opposite the AP site, but efficiently extends from nucleotides, particularly an A, inserted opposite the lesion.[1] [2] [3] [4] Publication Abstract from PubMedDNA polymerase zeta (Polzeta) belongs to the same B-family as high-fidelity replicative polymerases, yet is specialized for the extension reaction in translesion DNA synthesis (TLS). Despite its importance in TLS, the structure of Polzeta is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Polzeta holoenzyme in the act of DNA synthesis (3.1 A) and without DNA (4.1 A). Polzeta displays a pentameric ring-like architecture, with catalytic Rev3, accessory Pol31' Pol32 and two Rev7 subunits forming an uninterrupted daisy chain of protein-protein interactions. We also uncover the features that impose high fidelity during the nucleotide-incorporation step and those that accommodate mismatches and lesions during the extension reaction. Collectively, we decrypt the molecular underpinnings of Polzeta's role in TLS and provide a framework for new cancer therapeutics. Structure and mechanism of B-family DNA polymerase zeta specialized for translesion DNA synthesis.,Malik R, Kopylov M, Gomez-Llorente Y, Jain R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK Nat Struct Mol Biol. 2020 Oct;27(10):913-924. doi: 10.1038/s41594-020-0476-7., Epub 2020 Aug 17. PMID:32807989[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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