Multiple pathways inhibit NHEJ at telomeres.
The nonhomologous end-joining (NHEJ) repair pathway 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. 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 origin recognition complex (ORC) subunit.
Marcand
Stéphane
S
Centre National de la Recherche Scientifque UMR 217, Institut de Radiobiologie Cellulaire et Moléculaire, CEA/Fontenay, 92265 Fontenay-aux-roses cedex, France. stephane.marcand@cea.fr
Pardo
Benjamin
B
Gratias
Ariane
A
Cahun
Sabrina
S
Callebaut
Isabelle
I
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics; D004260:DNA Repair; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011995:Recombination, Genetic / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D000089804:Shelterin Complex; D015398:Signal Transduction; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D002352:Carrier Proteins; C440829:RAP1 protein, S cerevisiae; C105362:RIF2 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D034501:Telomere-Binding Proteins; D014157:Transcription Factors