8S8P

Restriction on Ku Inward Translocation Caps Telomere Ends

Summary for 8S8P

• Entry DOI: 10.2210/pdb8s8p/pdb
• Related: 8S82
• EMDB information: 19811
• Descriptor: DNA (5'-D(*AP*CP*AP*CP*AP*CP*AP*CP*AP*CP*CP*CP*AP*CP*AP*CP*AP*CP*CP*AP*C)-3'), 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'), ATP-dependent DNA helicase II subunit 1, ... (5 entities in total)
• Functional Keywords: telomere, nhej, rap1, ku, chromosome, dna repair, mutagenesis, dna binding protein
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 5
• Total formula weight: 173256.96

Authors

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. (deposition date: 2024-03-07, release date: 2025-06-18, Last modification date: 2025-08-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.11 Å)