4NDH

Human Aprataxin (Aptx) bound to DNA, AMP, and Zn - product complex

4NDH の概要

• エントリーDOI: 10.2210/pdb4ndh/pdb
• 関連するPDBエントリー: 3SZQ 4NDF 4NDG 4NDI
• 分子名称: Aprataxin, 5'-D(P*GP*TP*TP*CP*TP*AP*GP*AP*AP*C)-3', ADENOSINE MONOPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: protein-dna complex, dna repair, 5'-dna end processing, histidine triad domain, hit domain, zinc finger, 5'-dna end recognition, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus, nucleoplasm. Isoform 12: Cytoplasm: Q7Z2E3
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 55520.84

構造登録者

Schellenberg, M.J.,Tumbale, P.S.,Williams, R.S. (登録日: 2013-10-26, 公開日: 2013-12-18, 最終更新日: 2023-09-20)

主引用文献

Tumbale, P.,Williams, J.S.,Schellenberg, M.J.,Kunkel, T.A.,Williams, R.S.
Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.
Nature, 506:111-115, 2013

PubMed Abstract: Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases. Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5'-adenylated (5'-AMP) DNA lesions. Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5' ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA-DNA, and acting in an RNA-DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure-function studies of human APTX-RNA-DNA-AMP-Zn complexes define a mechanism for detecting and reversing adenylation at RNA-DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA-DNA may contribute to neurological disease.

PubMed: 24362567
DOI: 10.1038/nature12824

実験手法

X-RAY DIFFRACTION (1.848 Å)