Multiple pathways inhibit NHEJ at telomeres

Stéphane Marcand (1) , Benjamin Pardo (1, 2) , Ariane Gratias (1, 3) , Sabrina Cahun (1) , Isabelle Callebaut (4)

1 IRCM - Institut de Radiobiologie Cellulaire et Moléculaire
2 Department of Molecular Biology
3 UP11 - Université Paris-Sud - Paris 11
4 IMPMC - Institut de minéralogie et de physique des milieux condensés

The non-homologous end joining repair pathway (NHEJ) is inhibited at telomeres, preventing chromosome fusion. In budding yeast Saccharomyces cerevisiae, the Rap1 protein directly binds the telomere sequences and is required for NHEJ inhibition. Here we show that the Rap1 C-terminal domain establishes two parallel inhibitory pathways through the proteins Rif2 and Sir4 respectively. In addition, the central domain of Rap1 inhibits NHEJ independently of Rif2 and Sir4. Thus Rap1 establishes several independent pathways to prevent telomere fusions. We discuss a possible mechanism that would explain Rif2 multifunctionality at telomeres and the recent evolutionary origin of Rif2 from an ORC subunit.

Domaines: Biochimie, Biologie Moléculaire

Stéphane Marcand, Benjamin Pardo, Ariane Gratias, Sabrina Cahun, Isabelle Callebaut. Multiple pathways inhibit NHEJ at telomeres. Genes and Development, 2008, pp.1153-1158. ⟨hal-00261858⟩