6M7V

Human DNA polymerase eta extension complex with cdA at the -1 position

6M7V の概要

• エントリーDOI: 10.2210/pdb6m7v/pdb
• 分子名称: DNA polymerase eta, DNA (5'-D(P*GP*TP*GP*TP*GP*AP*GP*T)-3'), DNA (5'-D(P*(02I)P*CP*TP*CP*AP*CP*AP*CP*T)-3'), ... (7 entities in total)
• 機能のキーワード: translesion synthesis, human dna polymerse eta cda, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 54431.88

構造登録者

Weng, P.,Gao, Y.,Yang, W. (登録日: 2018-08-21, 公開日: 2018-09-12, 最終更新日: 2023-10-11)

主引用文献

Weng, P.J.,Gao, Y.,Gregory, M.T.,Wang, P.,Wang, Y.,Yang, W.
Bypassing a 8,5'-cyclo-2'-deoxyadenosine lesion by human DNA polymerase eta at atomic resolution.
Proc. Natl. Acad. Sci. U.S.A., 115:10660-10665, 2018

PubMed Abstract: Oxidatively induced DNA lesions 8,5'-cyclopurine-2'-deoxynucleosides (cdPus) are prevalent and cytotoxic by impeding DNA replication and transcription. Both the 5'- and 5'-diastereomers of cdPu can be removed by nucleotide excision repair; however, the 5'-cdPu is more resistant to repair than the 5' counterpart. Here, we report the crystal structures of human polymerase (Pol) η bypassing 5'-8,5'-cyclo-2'-deoxyadenosine (cdA) in insertion and the following two extension steps. The cdA-containing DNA structures vary in response to the protein environment. Supported by the "molecular splint" of Pol η, the structure of 5'-cdA at 1.75-Å resolution reveals that the backbone is pinched toward the minor groove and the adenine base is tilted. In the templating position, the cdA takes up the extra space usually reserved for the thymine dimer, and dTTP is efficiently incorporated by Pol η in the presence of Mn Rigid distortions of the DNA duplex by cdA, however, prevent normal base pairing and hinder immediate primer extension by Pol η. Our results provide structural insights into the strong replication blockage effect and the mutagenic property of the cdPu lesions in cells.

PubMed: 30275308
DOI: 10.1073/pnas.1812856115

実験手法

X-RAY DIFFRACTION (3.062 Å)