7LT3

NHEJ Long-range synaptic complex

7LT3 の概要

• エントリーDOI: 10.2210/pdb7lt3/pdb
• EMDBエントリー: 23510
• 分子名称: X-ray repair cross-complementing protein 6, ADENOSINE-5'-DIPHOSPHATE, X-ray repair cross-complementing protein 5, ... (10 entities in total)
• 機能のキーワード: nhej, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 1714995.47

構造登録者

He, Y.,Chen, S. (登録日: 2021-02-18, 公開日: 2021-04-14, 最終更新日: 2024-03-06)

主引用文献

Chen, S.,Lee, L.,Naila, T.,Fishbain, S.,Wang, A.,Tomkinson, A.E.,Lees-Miller, S.P.,He, Y.
Structural basis of long-range to short-range synaptic transition in NHEJ.
Nature, 593:294-298, 2021

PubMed Abstract: DNA double-strand breaks (DSBs) are a highly cytotoxic form of DNA damage and the incorrect repair of DSBs is linked to carcinogenesis. The conserved error-prone non-homologous end joining (NHEJ) pathway has a key role in determining the effects of DSB-inducing agents that are used to treat cancer as well as the generation of the diversity in antibodies and T cell receptors. Here we applied single-particle cryo-electron microscopy to visualize two key DNA-protein complexes that are formed by human NHEJ factors. The Ku70/80 heterodimer (Ku), the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), DNA ligase IV (LigIV), XRCC4 and XLF form a long-range synaptic complex, in which the DNA ends are held approximately 115 Å apart. Two DNA end-bound subcomplexes comprising Ku and DNA-PKcs are linked by interactions between the DNA-PKcs subunits and a scaffold comprising LigIV, XRCC4, XLF, XRCC4 and LigIV. The relative orientation of the DNA-PKcs molecules suggests a mechanism for autophosphorylation in trans, which leads to the dissociation of DNA-PKcs and the transition into the short-range synaptic complex. Within this complex, the Ku-bound DNA ends are aligned for processing and ligation by the XLF-anchored scaffold, and a single catalytic domain of LigIV is stably associated with a nick between the two Ku molecules, which suggests that the joining of both strands of a DSB involves both LigIV molecules.

PubMed: 33854234
DOI: 10.1038/s41586-021-03458-7

実験手法

ELECTRON MICROSCOPY (4.6 Å)