4QZA

Mouse Tdt in complex with a DSB substrate, C-C base pair

4QZA の概要

• エントリーDOI: 10.2210/pdb4qza/pdb
• 関連するPDBエントリー: 1JMS 4I27 4QZ8 4QZ9 4QZB 4QZC 4QZD 4QZE 4QZF 4QZG 4QZH 4QZI
• 分子名称: DNA nucleotidylexotransferase, 5'-D(*AP*AP*AP*AP*AP*C)-3', 5'-D(*TP*TP*TP*TP*TP*GP*C)-3', ... (7 entities in total)
• 機能のキーワード: terminal deoxynucleotidyltransferase, nucleus, transferase-dna complex, transferase/dna
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Isoform TDT-S: Nucleus. Isoform TDT-L: Cytoplasm. Nucleus : P09838
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 52392.83

構造登録者

Gouge, J.,Delarue, M. (登録日: 2014-07-27, 公開日: 2015-06-10, 最終更新日: 2023-09-20)

主引用文献

Gouge, J.,Rosario, S.,Romain, F.,Poitevin, F.,Beguin, P.,Delarue, M.
Structural basis for a novel mechanism of DNA bridging and alignment in eukaryotic DSB DNA repair.
Embo J., 34:1126-1142, 2015

PubMed Abstract: Eukaryotic DNA polymerase mu of the PolX family can promote the association of the two 3'-protruding ends of a DNA double-strand break (DSB) being repaired (DNA synapsis) even in the absence of the core non-homologous end-joining (NHEJ) machinery. Here, we show that terminal deoxynucleotidyltransferase (TdT), a closely related PolX involved in V(D)J recombination, has the same property. We solved its crystal structure with an annealed DNA synapsis containing one micro-homology (MH) base pair and one nascent base pair. This structure reveals how the N-terminal domain and Loop 1 of Tdt cooperate for bridging the two DNA ends, providing a templating base in trans and limiting the MH search region to only two base pairs. A network of ordered water molecules is proposed to assist the incorporation of any nucleotide independently of the in trans templating base. These data are consistent with a recent model that explains the statistics of sequences synthesized in vivo by Tdt based solely on this dinucleotide step. Site-directed mutagenesis and functional tests suggest that this structural model is also valid for Pol mu during NHEJ.

PubMed: 25762590
DOI: 10.15252/embj.201489643

実験手法

X-RAY DIFFRACTION (2.15 Å)