4B9M

Structure of the high fidelity DNA polymerase I with an oxidative formamidopyrimidine-dA DNA lesion -thymine basepair in the post- insertion site.

Summary for 4B9M

• Entry DOI: 10.2210/pdb4b9m/pdb
• Related: 2XO7 2XY5 2XY6 2XY7 2Y1I 2Y1J 4B9L 4B9N 4B9S 4B9T 4B9U 4B9V
• Descriptor: DNA POLYMERASE I, 5'-D(*GP*CP*CP*TP*GP*AP*CP*TP*CP*TP*TP)-3', 5'-D(*DC*DA*DA*FAX*AP*GP*AP*GP*TP*CP*AP*GP*GP*CP*TP)-3', ... (6 entities in total)
• Functional Keywords: transferase-dna complex, oxidative dna lesion, dna damage, translesion dna synthesis, replication, transferase/dna
• Biological source: GEOBACILLUS STEAROTHERMOPHILUS; More
• Total number of polymer chains: 3
• Total formula weight: 78990.51

Authors

Gehrke, T.H.,Lischke, U.,Arnold, S.,Schneider, S.,Carell, T. (deposition date: 2012-09-05, release date: 2013-04-17, Last modification date: 2023-12-20)

Primary citation

Gehrke, T.H.,Lischke, U.,Gasteiger, K.L.,Schneider, S.,Arnold, S.,Muller, H.C.,Stephenson, D.S.,Zipse, H.,Carell, T.
Unexpected Non-Hoogsteen-Based Mutagenicity Mechanism of Fapy-DNA Lesions.
Nat.Chem.Biol., 9:455-, 2013

PubMed Abstract: 8-Oxopurines (8-oxodG and 8-oxodA) and formamidopyrimidines (FaPydG and FaPydA) are major oxidative DNA lesions involved in cancer development and aging. Their mutagenicity is believed to result from a conformational shift of the N9-C1' glycosidic bonds from anti to syn, which allows the lesions to form noncanonical Hoogsteen-type base pairs with incoming triphosphates during DNA replication. Here we present biochemical data and what are to our knowledge the first crystal structures of carbocyclic FaPydA and FaPydG containing DNA in complex with a high-fidelity polymerase. Crystallographic snapshots show that the cFaPy lesions keep the anti geometry of the glycosidic bond during error-free and error-prone replication. The observed dG·dC→dT·dA transversion mutations are the result of base shifting and tautomerization.

PubMed: 23685671
DOI: 10.1038/NCHEMBIO.1254

Experimental method

X-RAY DIFFRACTION (2.05 Å)