6ABO

human XRCC4 and IFFO1 complex

6ABO の概要

• エントリーDOI: 10.2210/pdb6abo/pdb
• 分子名称: DNA repair protein XRCC4, Intermediate filament family orphan 1, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: complex, coiled-coil, nuclear protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36246.86

構造登録者

Li, J.,Liu, L.,Liang, H.,Liu, Y.,Xu, D. (登録日: 2018-07-23, 公開日: 2019-07-31, 最終更新日: 2023-11-22)

主引用文献

Li, W.,Bai, X.,Li, J.,Zhao, Y.,Liu, J.,Zhao, H.,Liu, L.,Ding, M.,Wang, Q.,Shi, F.Y.,Hou, M.,Ji, J.,Gao, G.,Guo, R.,Sun, Y.,Liu, Y.,Xu, D.
The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses chromosome translocation during tumorigenesis.
Nat.Cell Biol., 21:1273-1285, 2019

PubMed Abstract: Chromosome translocation is a major cause of the onset and progression of diverse types of cancers. However, the mechanisms underlying this process remain poorly understood. Here, we identified a non-homologous end-joining protein, IFFO1, which structurally forms a heterotetramer with XRCC4. IFFO1 is recruited to the sites of DNA damage by XRCC4 and promotes the repair of DNA double-strand breaks in a parallel pathway with XLF. Interestingly, IFFO1 interacts with lamin A/C, forming an interior nucleoskeleton. Inactivating IFFO1 or its interaction with XRCC4 or lamin A/C leads to increases in both the mobility of broken ends and the frequency of chromosome translocation. Importantly, the destruction of this nucleoskeleton accounts for the elevated frequency of chromosome translocation in many types of cancer cells. Our results reveal that the lamin A/C-IFFO1-constituted nucleoskeleton prevents chromosome translocation by immobilizing broken DNA ends during tumorigenesis.

PubMed: 31548606
DOI: 10.1038/s41556-019-0388-0

実験手法

X-RAY DIFFRACTION (2.65 Å)