6ABO

human XRCC4 and IFFO1 complex

Summary for 6ABO

• Entry DOI: 10.2210/pdb6abo/pdb
• Descriptor: DNA repair protein XRCC4, Intermediate filament family orphan 1, GLYCEROL, ... (5 entities in total)
• Functional Keywords: complex, coiled-coil, nuclear protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 36246.86

Authors

Li, J.,Liu, L.,Liang, H.,Liu, Y.,Xu, D. (deposition date: 2018-07-23, release date: 2019-07-31, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.65 Å)