2DY4

Crystal structure of RB69 GP43 in complex with DNA containing Thymine Glycol

Summary for 2DY4

• Entry DOI: 10.2210/pdb2dy4/pdb
• Related: 1CLQ 1IG9 1Q9X 1Q9Y 1RV2 2DTU
• Descriptor: 5'-D(*CP*GP*(CTG)P*GP*GP*AP*AP*TP*GP*A*CP*AP*GP*CP*CP*GP*CP*G)-3', 5'-D(*GP*CP*GP*GP*CP*TP*GP*T*CP*AP*TP*TP*CP*CP*A)-3', DNA polymerase, ... (4 entities in total)
• Functional Keywords: dna polymerase, dna lesion, thymine glycol, oxidative thymine lesion, transferase-dna complex, transferase/dna
• Biological source: Enterobacteria phage RB69
• Total number of polymer chains: 12
• Total formula weight: 463956.60

Authors

Aller, P.,Rould, M.A.,Hogg, M.,Wallace, S.S.,Doublie, S. (deposition date: 2006-09-06, release date: 2007-01-09, Last modification date: 2024-10-23)

Primary citation

Aller, P.,Rould, M.A.,Hogg, M.,Wallace, S.S.,Doublie, S.
A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycol.
Proc.Natl.Acad.Sci.USA, 104:814-818, 2007

PubMed Abstract: Thymine glycol (Tg) is a common product of oxidation and ionizing radiation, including that used for cancer treatment. Although Tg is a poor mutagenic lesion, it has been shown to present a strong block to both repair and replicative DNA polymerases. The 2.65-A crystal structure of a binary complex of the replicative RB69 DNA polymerase with DNA shows that the templating Tg is intrahelical and forms a regular Watson-Crick base pair with the incorporated A. The C5 methyl group protrudes axially from the ring of the damaged pyrimidine and hinders stacking of the adjacent 5' template guanine. The position of the displaced 5' template guanine is such that the next incoming nucleotide cannot be incorporated into the growing primer strand, and it explains why primer extension past the lesion is prohibited even though DNA polymerases can readily incorporate an A across from the Tg lesion.

PubMed: 17210917
DOI: 10.1073/pnas.0606648104

Experimental method

X-RAY DIFFRACTION (2.65 Å)