Structural highlights
5wm1 is a 3 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , |
| NonStd Res: | |
| Gene: | REV1, YOR346W, O6339 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[REV1_YEAST] Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents. Involved in mitochondrial DNA mutagenesis.[1] [2] [3]
Publication Abstract from PubMed
Benzo[a]pyrene (BP) is a carcinogen in cigarette smoke which, after metabolic activation, can react with the exocyclic N 2 amino group of guanine to generate four stereoisomeric BP-N 2-dG adducts. Rev1 is unique among translesion synthesis DNA polymerases in employing a protein-template-directed mechanism of DNA synthesis opposite undamaged and damaged guanine. Here we report high-resolution structures of yeast Rev1 with three BP-N 2-dG adducts, namely the 10S (+)-trans-BP-N 2-dG, 10R (+)-cis-BP-N 2-dG, and 10S ( - )-cis-BP-N 2-dG. Surprisingly, in all three structures, the bulky and hydrophobic BP pyrenyl residue is entirely solvent-exposed in the major groove of the DNA. This is very different from the adduct alignments hitherto observed in free or protein-bound DNA. All complexes are well poised for dCTP insertion. Our structures provide a view of cis-BP-N 2-dG adducts in a DNA polymerase active site, and offer a basis for understanding error-free replication of the BP-derived stereoisomeric guanine adducts.Benzo[a]pyrene (BP) is a carcinogen in cigarette smoke that upon metabolic activation reacts with guanine. Here, the authors present the structures of the translesion DNA synthesis polymerase Rev1 in complex with three of the four possible stereoisomeric BP-N 2 -dG adducts, which gives insights how Rev1 achieves error-free replication.
Mechanism of error-free replication across benzo[a]pyrene stereoisomers by Rev1 DNA polymerase.,Rechkoblit O, Kolbanovskiy A, Landes H, Geacintov NE, Aggarwal AK Nat Commun. 2017 Oct 17;8(1):965. doi: 10.1038/s41467-017-01013-5. PMID:29042535[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nelson JR, Lawrence CW, Hinkle DC. Deoxycytidyl transferase activity of yeast REV1 protein. Nature. 1996 Aug 22;382(6593):729-31. PMID:8751446 doi:10.1038/382729a0
- ↑ 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
- ↑ Rechkoblit O, Kolbanovskiy A, Landes H, Geacintov NE, Aggarwal AK. Mechanism of error-free replication across benzo[a]pyrene stereoisomers by Rev1 DNA polymerase. Nat Commun. 2017 Oct 17;8(1):965. doi: 10.1038/s41467-017-01013-5. PMID:29042535 doi:http://dx.doi.org/10.1038/s41467-017-01013-5
