6P94

Human APE1 C65A AP-endonuclease product complex

6P94 の概要

• エントリーDOI: 10.2210/pdb6p94/pdb
• 関連するPDBエントリー: 6P93
• 分子名称: DNA-(apurinic or apyrimidinic site) lyase, DNA (5'-D(P*(3DR)P*CP*GP*AP*CP*GP*GP*AP*TP*CP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*C)-3'), ... (9 entities in total)
• 機能のキーワード: ape1, nuclease, dna repair, dna binding protein, lyase-dna complex, lyase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 75463.36

構造登録者

Whitaker, A.W.,Stark, W.J.,Freudenthal, B.D. (登録日: 2019-06-09, 公開日: 2020-01-01, 最終更新日: 2023-10-11)

主引用文献

McNeill, D.R.,Whitaker, A.M.,Stark, W.J.,Illuzzi, J.L.,McKinnon, P.J.,Freudenthal, B.D.,Wilson, D.M.
Functions of the major abasic endonuclease (APE1) in cell viability and genotoxin resistance.
Mutagenesis, 35:27-38, 2020

PubMed Abstract: DNA is susceptible to a range of chemical modifications, with one of the most frequent lesions being apurinic/apyrimidinic (AP) sites. AP sites arise due to damage-induced (e.g. alkylation) or spontaneous hydrolysis of the N-glycosidic bond that links the base to the sugar moiety of the phosphodiester backbone, or through the enzymatic activity of DNA glycosylases, which release inappropriate bases as part of the base excision repair (BER) response. Unrepaired AP sites, which lack instructional information, have the potential to cause mutagenesis or to arrest progressing DNA or RNA polymerases, potentially causing outcomes such as cellular transformation, senescence or death. The predominant enzyme in humans responsible for repairing AP lesions is AP endonuclease 1 (APE1). Besides being a powerful AP endonuclease, APE1 possesses additional DNA repair activities, such as 3'-5' exonuclease, 3'-phophodiesterase and nucleotide incision repair. In addition, APE1 has been shown to stimulate the DNA-binding activity of a number of transcription factors through its 'REF1' function, thereby regulating gene expression. In this article, we review the structural and biochemical features of this multifunctional protein, while reporting on new structures of the APE1 variants Cys65Ala and Lys98Ala. Using a functional complementation approach, we also describe the importance of the repair and REF1 activities in promoting cell survival, including the proposed passing-the-baton coordination in BER. Finally, results are presented indicating a critical role for APE1 nuclease activities in resistance to the genotoxins methyl methanesulphonate and bleomycin, supporting biologically important functions as an AP endonuclease and 3'-phosphodiesterase, respectively.

PubMed: 31816044
DOI: 10.1093/mutage/gez046

実験手法

X-RAY DIFFRACTION (2.09 Å)