5V1N

DNA polymerase beta substrate complex with 8-oxoG:A at the primer terminus and incoming dCTP

5V1N の概要

• エントリーDOI: 10.2210/pdb5v1n/pdb
• 関連するPDBエントリー: 5vif 5vig 5vih 5vii 5vij 5vio 5vip 5vir
• 分子名称: DNA (5'-D(*CP*CP*GP*AP*CP*GP*AP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*(8OG))-3'), DNA (5'-D(P*GP*TP*CP*GP*G)-3'), ... (9 entities in total)
• 機能のキーワード: transferase ligase / dna, transferase-dna, ligase-dna complex, transferase/dna, ligase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 48389.10

構造登録者

Freudenthal, B.D.,Schaich, M.A.,Whitaker, A.M.,Smith, M.R. (登録日: 2017-03-02, 公開日: 2017-05-10, 最終更新日: 2024-03-06)

主引用文献

Whitaker, A.M.,Smith, M.R.,Schaich, M.A.,Freudenthal, B.D.
Capturing a mammalian DNA polymerase extending from an oxidized nucleotide.
Nucleic Acids Res., 45:6934-6944, 2017

PubMed Abstract: The oxidized nucleotide, 8-oxo-7,8-dihydro-2΄-deoxyguanosine (8-oxoG), is one of the most abundant DNA lesions. 8-oxoG plays a major role in tumorigenesis and human disease. Biological consequences of 8-oxoG are mediated in part by its insertion into the genome, making it essential to understand how DNA polymerases handle 8-oxoG. Insertion of 8-oxoG is mutagenic when opposite adenine but not when opposite cytosine. However, either result leads to DNA damage at the primer terminus (3΄-end) during the succeeding insertion event. Extension from DNA damage at primer termini remains poorly understood. Using kinetics and time-lapse crystallography, we evaluated how a model DNA polymerase, human polymerase β, accommodates 8-oxoG at the primer terminus opposite cytosine and adenine. Notably, extension from the mutagenic base pair is favored over the non-mutagenic base pair. When 8-oxoG is at the primer terminus opposite cytosine, DNA centric changes lead to a clash between O8 of 8-oxoG and the phosphate backbone. Changes in the extension reaction resulting from the altered active site provide evidence for a stabilizing interaction between Arg254 and Asp256 that serves an important role during DNA synthesis reactions. These results provide novel insights into the impact of damage at the primer terminus on genomic stability and DNA synthesis.

PubMed: 28449123
DOI: 10.1093/nar/gkx293

実験手法

X-RAY DIFFRACTION (2.005 Å)