7N3Y

Crystal Structure of Saccharomyces cerevisiae Apn2 Catalytic Domain E59Q/D222N Mutant in Complex with DNA

7N3Y の概要

• エントリーDOI: 10.2210/pdb7n3y/pdb
• 関連するPDBエントリー: 7N3Z
• 分子名称: DNA-(apurinic or apyrimidinic site) endonuclease 2, DNA (5'-D(*TP*CP*CP*GP*AP*AP*AP*TP*(PST)P*(PST)P*(SC)P*(GS)P*(GS))-3'), DNA (5'-D(*CP*CP*GP*AP*AP*AP*TP*TP*(PST)P*(SC)P*(GS)P*(GS)P*(AS))-3'), ... (9 entities in total)
• 機能のキーワード: nuclease, dna complex, eep fold, ape2 homolog, hydrolase, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 206379.71

構造登録者

Wojtaszek, J.L.,Krahn, J.,Wallace, B.D.,Williams, R.S. (登録日: 2021-06-02, 公開日: 2022-09-28, 最終更新日: 2023-10-18)

主引用文献

Williams, J.S.,Wojtaszek, J.L.,Appel, D.C.,Krahn, J.,Wallace, B.D.,Walsh, E.,Kunkel, T.A.,Williams, R.S.
Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2.
Cell Rep, 41:111448-111448, 2022

PubMed Abstract: Topoisomerase 1 (Top1) incises DNA containing ribonucleotides to generate complex DNA lesions that are resolved by APE2 (Apn2 in yeast). How Apn2 engages and processes this DNA damage is unclear. Here, we report X-ray crystal structures and biochemical analysis of Apn2-DNA complexes to demonstrate how Apn2 frays and cleaves 3' DNA termini via a wedging mechanism that facilitates 1-6 nucleotide endonucleolytic cleavages. APN2 deletion and DNA-wedge mutant Saccharomyces cerevisiae strains display mutator phenotypes, cell growth defects, and sensitivity to genotoxic stress in a ribonucleotide excision repair (RER)-defective background harboring a high density of Top1-incised ribonucleotides. Our data implicate a wedge-and-cut mechanism underpinning the broad-specificity Apn2 nuclease activity that mitigates mutagenic and genome instability phenotypes caused by Top1 incision at genomic ribonucleotides incorporated by DNA polymerase epsilon.

PubMed: 36198268
DOI: 10.1016/j.celrep.2022.111448

実験手法

X-RAY DIFFRACTION (2.73 Å)