Article
- The EMBO Journal (2005) 24, 3117 - 3127
- doi:10.1038/sj.emboj.7600778
Published online: 11 August 2005
Subject Category:
Rap1 prevents telomere fusions by nonhomologous end joining
Benjamin Pardo1,2 and Stéphane Marcand1,2
- Laboratoire de Radiobiologie de l'ADN, Service de Radiobiologie Moléculaire et Cellulaire, CEA/Fontenay, Fontenay aux Roses, France
- Laboratoire du Contrôle du Cycle Cellulaire, Service de Biochimie et de Génétique Moléculaire, CEA/Saclay, Gif sur Yvette, France
Correspondence to:
Stéphane Marcand, CEA/Far, UMR217-DSV/DRR/SRMC Laboratoire de Radiobiologie de l'ADN, 92265 Fontenay aux Roses Cedex, France. Tel.: +33 1 46 54 82 33; Fax: +33 1 46 54 91 80; E-mail: stephane.marcand@cea.fr
Received 28 February 2005; Accepted 19 July 2005
Abstract
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.
Keywords:
- ATM,
- chromosome fusion,
- genomic instability,
- NHEJ,
- telomere
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