5IIK

Crystal structure of the post-catalytic nick complex of DNA polymerase lambda with a templating 8-oxo-dG and incorporated dC

5IIK の概要

• エントリーDOI: 10.2210/pdb5iik/pdb
• 関連するPDBエントリー: 5III 5IIJ 5IIL 5IIM 5IIN 5IIO
• 分子名称: DNA polymerase lambda, DNA (5'-D(P*GP*CP*CP*G)-3'), DNA (5'-D(*CP*AP*GP*TP*AP*CP*T)-3'), ... (7 entities in total)
• 機能のキーワード: transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: Q9UGP5
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 44266.10

構造登録者

Burak, M.J.,Guja, K.E.,Garcia-Diaz, M. (登録日: 2016-03-01, 公開日: 2016-08-17, 最終更新日: 2024-03-06)

主引用文献

Burak, M.J.,Guja, K.E.,Hambardjieva, E.,Derkunt, B.,Garcia-Diaz, M.
A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG.
Embo J., 35:2045-2059, 2016

PubMed Abstract: 8-oxo-7,8-dihydroxy-2'-deoxyguanosine (8-oxo-dG) has high mutagenic potential as it is prone to mispair with deoxyadenine (dA). In order to maintain genomic integrity, post-replicative 8-oxo-dG:dA mispairs are removed through DNA polymerase lambda (Pol λ)-dependent MUTYH-initiated base excision repair (BER). Here, we describe seven novel crystal structures and kinetic data that fully characterize 8-oxo-dG bypass by Pol λ. We demonstrate that Pol λ has a flexible active site that can tolerate 8-oxo-dG in either the anti- or syn-conformation. Importantly, we show that discrimination against the pro-mutagenic syn-conformation occurs at the extension step and identify the residue responsible for this selectivity. This residue acts as a kinetic switch, shunting repair toward long-patch BER upon correct dCMP incorporation, thus enhancing repair efficiency. Moreover, this switch also provides a potential mechanism to increase repair fidelity of MUTYH-initiated BER.

PubMed: 27481934
DOI: 10.15252/embj.201694332

実験手法

X-RAY DIFFRACTION (1.982 Å)