2R8J

Structure of the Eukaryotic DNA Polymerase eta in complex with 1,2-d(GpG)-cisplatin containing DNA

2R8J の概要

• エントリーDOI: 10.2210/pdb2r8j/pdb
• 関連するPDBエントリー: 1JIH 2R8K
• 分子名称: DNA (5'-D(*DGP*DTP*DGP*DGP*DAP*DTP*DGP*DAP*DG)-3'), DNA (5'-D(P*DGP*DGP*DCP*DTP*DCP*DAP*DTP*DCP*DCP*DAP*DC)-3'), DNA polymerase eta, ... (7 entities in total)
• 機能のキーワード: protein-cisplatin-dna-dntp complex, replication, transferase-dna complex, transferase/dna
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Nucleus: Q04049
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 139190.34

構造登録者

Carell, T.,Alt, A.,Lammens, K. (登録日: 2007-09-11, 公開日: 2007-12-11, 最終更新日: 2023-08-30)

主引用文献

Alt, A.,Lammens, K.,Chiocchini, C.,Lammens, A.,Pieck, J.C.,Kuch, D.,Hopfner, K.P.,Carell, T.
Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta
Science, 318:967-970, 2007

PubMed Abstract: DNA polymerase eta (Pol eta) is a eukaryotic lesion bypass polymerase that helps organisms to survive exposure to ultraviolet (UV) radiation, and tumor cells to gain resistance against cisplatin-based chemotherapy. It allows cells to replicate across cross-link lesions such as 1,2-d(GpG) cisplatin adducts (Pt-GG) and UV-induced cis-syn thymine dimers. We present structural and biochemical analysis of how Pol eta copies Pt-GG-containing DNA. The damaged DNA is bound in an open DNA binding rim. Nucleotidyl transfer requires the DNA to rotate into an active conformation, driven by hydrogen bonding of the templating base to the dNTP. For the 3'dG of the Pt-GG, this step is accomplished by a Watson-Crick base pair to dCTP and is biochemically efficient and accurate. In contrast, bypass of the 5'dG of the Pt-GG is less efficient and promiscuous for dCTP and dATP as a result of the presence of the rigid Pt cross-link. Our analysis reveals the set of structural features that enable Pol eta to replicate across strongly distorting DNA lesions.

PubMed: 17991862
DOI: 10.1126/science.1148242

実験手法

X-RAY DIFFRACTION (3.1 Å)