4REA

A Nuclease DNA complex

4REA の概要

• エントリーDOI: 10.2210/pdb4rea/pdb
• 関連するPDBエントリー: 4REB 4REC
• 分子名称: Fanconi-associated nuclease 1, DNA (5'-D(*TP*GP*CP*TP*CP*GP*CP*CP*AP*C)-3'), DNA (5'-D(P*CP*GP*TP*GP*GP*CP*GP*AP*GP*C)-3'), ... (4 entities in total)
• 機能のキーワード: hjc, tpr, sap, structural specific nuclease, fancd2, nucleus, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : Q9Y2M0
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 158589.08

構造登録者

Zhao, Q.,Xue, X.,Longerich, S.,Sung, P.,Xiong, Y. (登録日: 2014-09-22, 公開日: 2014-12-24, 最終更新日: 2024-02-28)

主引用文献

Zhao, Q.,Xue, X.,Longerich, S.,Sung, P.,Xiong, Y.
Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer.
Nat Commun, 5:5726-5726, 2014

PubMed Abstract: Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5' flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA and unwind a 5' flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1.

PubMed: 25500724
DOI: 10.1038/ncomms6726

実験手法

X-RAY DIFFRACTION (3.81 Å)