5JUM

Crystal Structure of Human DNA Polymerase Eta Inserting dCTP Opposite N-(2'-deoxyguanosin-8- yl)-3-aminobenzanthrone (C8-dG-ABA)

Summary for 5JUM

• Entry DOI: 10.2210/pdb5jum/pdb
• Related: 4O3N
• Descriptor: DNA polymerase eta, DNA (5'-D(*C*AP*TP*(4E9)P*AP*TP*GP*AP*CP*GP*CP*T)-3'), DNA (5'-D(*AP*GP*CP*GP*TP*CP*AP*T)-3'), ... (7 entities in total)
• Functional Keywords: environmental carcinogen, catalytic domain, protein, dna, dna damage, dna-directed dna polymerase, guanosine triphosphate, y-family polymerase, trans-lesion synthesis (tls), polymerase eta, dna binding, 3-nitrobenzanthrone, n-(2'-deoxyguanosin-8- yl)-3-aminobenzanthrone (c8-dg-aba)., transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 55681.49

Authors

Patra, A.,Politica, D.A.,Stone, M.P.,Egli, M. (deposition date: 2016-05-10, release date: 2016-09-07, Last modification date: 2023-09-27)

Primary citation

Patra, A.,Politica, D.A.,Chatterjee, A.,Tokarsky, E.J.,Suo, Z.,Basu, A.K.,Stone, M.P.,Egli, M.
Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase eta.
Chembiochem, 17:2033-2037, 2016

PubMed Abstract: The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of guanine (C8-dG-ABA). These adducts present a strong block to replicative polymerases but, remarkably, can be bypassed in a largely error-free manner by the human Y-family polymerase η (hPol η). Here, we report the crystal structure of a ternary Pol⋅DNA⋅dCTP complex between a C8-dG-ABA-containing template:primer duplex and hPol η. The complex was captured at the insertion stage and provides crucial insight into the mechanism of error-free bypass of this bulky lesion. Specifically, bypass involves accommodation of the ABA moiety inside a hydrophobic cleft to the side of the enzyme active site and formation of an intra-nucleotide hydrogen bond between the phosphate and ABA amino moiety, allowing the adducted guanine to form a standard Watson-Crick pair with the incoming dCTP.

PubMed: 27556902
DOI: 10.1002/cbic.201600420

Experimental method

X-RAY DIFFRACTION (2.6 Å)