Summary information and primary citation
- PDB-id
- 3rjj; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transferase, lyase-DNA
- Method
- X-ray (2.0 Å)
- Summary
- Ternary complex crystal structure of DNA polymerase beta with template 8odg provides insight into mutagenic lesion bypass
- Reference
- Batra VK, Shock DD, Beard WA, McKenna CE, Wilson SH (2012): "Binary complex crystal structure of DNA polymerase beta reveals multiple conformations of the templating 8-oxoguanine lesion." Proc.Natl.Acad.Sci.USA, 109, 113-118. doi: 10.1073/pnas.1112235108.
- Abstract
- Oxidation of genomic DNA forms the guanine lesion 7,8-dihydro-8-oxoguanine (8-oxoG). When in the template base position during DNA synthesis the 8-oxoG lesion has dual coding potential by virtue of its anti- and syn-conformations, base pairing with cytosine and adenine, respectively. This impacts mutagenesis, because insertion of adenine opposite template 8-oxoG can result in a G to T transversion. DNA polymerases vary by orders of magnitude in their preferences for mutagenic vs. error-free 8-oxoG lesion bypass. Yet, the structural basis for lesion bypass specificity is not well understood. The DNA base excision repair enzyme DNA polymerase (pol) β is presented with gap-filling synthesis opposite 8-oxoG during repair and has similar insertion efficiencies for dCTP and dATP. We report the structure of pol β in binary complex with template 8-oxoG in a base excision repair substrate. The structure reveals both the syn- and anti-conformations of template 8-oxoG in the confines of the polymerase active site, consistent with the dual coding observed kinetically for this enzyme. A ternary complex structure of pol β with the syn-8-oxoG:anti-A Hoogsteen base pair in the closed fully assembled preinsertion active site is also reported. The syn-conformation of 8-oxoG is stabilized by minor groove hydrogen bonding between the side chain of Arg283 and O8 of 8-oxoG. An adjustment in the position of the phosphodiester backbone 5'-phosphate enables 8-oxoG to adopt the syn-conformation.
