8S82

Restriction on Ku Inward Translocation Caps Telomere Ends

8S82 の概要

• エントリーDOI: 10.2210/pdb8s82/pdb
• 関連するPDBエントリー: 8RGO
• EMDBエントリー: 19790
• 分子名称: ATP-dependent DNA helicase II subunit 1, ATP-dependent DNA helicase II subunit 2, DNA (5'-D(*GP*TP*GP*GP*TP*GP*TP*GP*TP*GP*GP*GP*TP*GP*TP*GP*TP*GP*TP*GP*T)-3'), ... (4 entities in total)
• 機能のキーワード: telomere, nhej, rap1, ku, chromosome, dna repair, mutagenesis, dna binding protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 154957.50

構造登録者

Mattarocci, S.,Baconnais, S.,Roisne-Hamelin, F.,Pobiega, S.,Alibert, O.,Morin, V.,Deshayes, A.,Veaute, X.,Ropars, V.,Mazon, G.,Busso, D.,Fernandez Varela, P.,Le Cam, E.,Charbonnier, J.,Cuniasse, P.,Marcand, S. (登録日: 2024-03-05, 公開日: 2025-06-18, 最終更新日: 2025-08-13)

主引用文献

Mattarocci, S.,Baconnais, S.,Roisne-Hamelin, F.,Pobiega, S.,Alibert, O.,Morin, V.,Deshayes, A.,Veaute, X.,Ropars, V.,Chevreuil, M.,Mehringer, J.,Busso, D.,Mazon, G.,Fernandez Varela, P.,Le Cam, E.,Charbonnier, J.B.,Cuniasse, P.,Marcand, S.
Restriction of Ku translocation protects telomere ends.
Nat Commun, 16:6824-6824, 2025

PubMed Abstract: Safeguarding chromosome ends against fusions via nonhomologous end joining (NHEJ) is essential for genome integrity. Paradoxically, the conserved NHEJ core factor Ku binds telomere ends. How it is prevented from promoting NHEJ remains unclear, as does the mechanism that allows Ku to coexist with telomere-protective DNA binding proteins, Rap1 in Saccharomyces cerevisiae. Here, we find that Rap1 directly inhibits Ku's NHEJ function at telomeres. A single Rap1 molecule near a double-stand break suppresses NHEJ without displacing Ku in cells. Furthermore, Rap1 and Ku form a complex on short DNA duplexes in vitro. Cryo-EM shows Rap1 blocks Ku's inward translocation on DNA - an essential step for NHEJ at DSBs. Nanopore sequencing of telomere fusions confirms this mechanism protects native telomere ends. These findings uncover a telomere protection mechanism where Rap1 restricts Ku's inward translocation. This switches Ku from a repair-promoting to a protective role preventing NHEJ at telomeres.

PubMed: 40707444
DOI: 10.1038/s41467-025-61864-1

実験手法

ELECTRON MICROSCOPY (2.92 Å)