| Structural highlights
Function
DPOZ_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 PubMed
DNA 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 Also
References
- ↑ Haracska L, Unk I, Johnson RE, Johansson E, Burgers PM, Prakash S, Prakash L. Roles of yeast DNA polymerases delta and zeta and of Rev1 in the bypass of abasic sites. Genes Dev. 2001 Apr 15;15(8):945-54. PMID:11316789 doi:10.1101/gad.882301
- ↑ Zhang H, Chatterjee A, Singh KK. Saccharomyces cerevisiae polymerase zeta functions in mitochondria. Genetics. 2006 Apr;172(4):2683-8. Epub 2006 Feb 1. PMID:16452144 doi:genetics.105.051029
- ↑ Morrison A, Christensen RB, Alley J, Beck AK, Bernstine EG, Lemontt JF, Lawrence CW. REV3, a Saccharomyces cerevisiae gene whose function is required for induced mutagenesis, is predicted to encode a nonessential DNA polymerase. J Bacteriol. 1989 Oct;171(10):5659-67. PMID:2676986 doi:10.1128/jb.171.10.5659-5667.1989
- ↑ Nelson JR, Lawrence CW, Hinkle DC. Thymine-thymine dimer bypass by yeast DNA polymerase zeta. Science. 1996 Jun 14;272(5268):1646-9. PMID:8658138 doi:10.1126/science.272.5268.1646
- ↑ Malik R, Kopylov M, Gomez-Llorente Y, Jain R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK. Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis. Nat Struct Mol Biol. 2020 Oct;27(10):913-924. PMID:32807989 doi:10.1038/s41594-020-0476-7
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