3RJE

Ternary complex of DNA Polymerase Beta with a gapped DNA containing 8odG at template position

Summary for 3RJE

• Entry DOI: 10.2210/pdb3rje/pdb
• Related: 3RJF 3RJG 3RJH 3RJI 3RJJ 3RJK
• Descriptor: DNA polymerase beta, DNA (5'-D(*CP*CP*GP*AP*CP*(8OG)P*TP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*A)-3'), ... (6 entities in total)
• Functional Keywords: mutagenesis, g-t transversion, dna polymerase, oxidative damage, transferase, lyase-dna complex, lyase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P06746
• Total number of polymer chains: 4
• Total formula weight: 47814.84

Authors

Batra, V.K.,Beard, W.A.,Wilson, S.H. (deposition date: 2011-04-15, release date: 2012-01-18, Last modification date: 2023-09-13)

Primary citation

Batra, V.K.,Shock, D.D.,Beard, W.A.,McKenna, C.E.,Wilson, S.H.
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, 2012

PubMed 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.

PubMed: 22178760
DOI: 10.1073/pnas.1112235108

Experimental method

X-RAY DIFFRACTION (2.1 Å)