Rap1 prevents telomere fusions by nonhomologous end joining.
Telomeres protect chromosomes from end-to-end fusions. In yeast Saccharomyces cerevisiae, the protein Rap1 directly binds telomeric DNA. Here, we use a new conditional allele of RAP1 and show that Rap1 loss results in frequent fusions between telomeres. Analysis of the fusion point with restriction enzymes indicates that fusions occur between telomeres of near wild-type length. Telomere fusions are not observed in cells lacking factors required for nonhomologous end joining (NHEJ), including Lig4 (ligase IV), KU and the Mre11 complex. SAE2 and TEL1 do not affect the frequency of fusions. Together, these results show that Rap1 is essential to block NHEJ between telomeres. Since the presence of Rap1 at telomeres has been conserved through evolution, the establishment of NHEJ suppression by Rap1 could be universal.
Pardo
Benjamin
B
Laboratoire de Radiobiologie de l'ADN, Service de Radiobiologie Moléculaire et Cellulaire, CEA/Fontenay, Fontenay aux Roses, France.
Marcand
Stéphane
S
D002470:Cell Survival / Q000502:physiology; D015825:Chromosomes, Fungal / Q000235:genetics; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D004260:DNA Repair; D004262:DNA Restriction Enzymes / Q000737:chemistry; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004720:Endonucleases; D005090:Exodeoxyribonucleases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000089804:Shelterin Complex; D016615:Telomere / Q000235:genetics / Q000502:physiology*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
C000607891:DNL4 protein, S cerevisiae; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C440829:RAP1 protein, S cerevisiae; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; D004262:DNA Restriction Enzymes; D011088:DNA Ligases; D000072481:DNA Ligase ATP