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TitleRestriction of Ku translocation protects telomere ends.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 6824, Year 2025
Publish dateJul 24, 2025
AuthorsStefano Mattarocci / Sonia Baconnais / Florian Roisné-Hamelin / Sabrina Pobiega / Olivier Alibert / Vincent Morin / Alice Deshayes / Xavier Veaute / Virginie Ropars / Maelenn Chevreuil / Johannes Mehringer / Didier Busso / Gerard Mazon / Paloma Fernandez Varela / Éric Le Cam / Jean-Baptiste Charbonnier / Philippe Cuniasse / Stéphane Marcand /
PubMed AbstractSafeguarding 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 ...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.
External linksNat Commun / PubMed:40707444 / PubMed Central
MethodsEM (single particle)
Resolution2.92 - 3.11 Å
Structure data

19790

8s82

EMDB-19790, PDB-8s82:
Restriction on Ku Inward Translocation Caps Telomere Ends
Method: EM (single particle) / Resolution: 2.92 Å

19811

8s8p

EMDB-19811, PDB-8s8p:
Restriction on Ku Inward Translocation Caps Telomere Ends
Method: EM (single particle) / Resolution: 3.11 Å

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / Telomere / NHEJ / Rap1 / Ku / Chromosome / DNA Repair / Mutagenesis

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