This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Ruiz, J. F.
Right arrow Articles by Aguilera, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ruiz, J. F.
Right arrow Articles by Aguilera, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2009, p. 5441-5454, Vol. 29, No. 20
0270-7306/09/$08.00+0     doi:10.1128/MCB.00256-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Chromosomal Translocations Caused by Either Pol32-Dependent or Pol32-Independent Triparental Break-Induced Replication{triangledown} ,{dagger}

José F. Ruiz, Belén Gómez-González, and Andrés Aguilera*

Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Av. Américo Vespucio s/n, 41092 Sevilla, Spain

Received 26 February 2009/ Returned for modification 5 April 2009/ Accepted 28 July 2009

Double-strand breaks (DSBs) are harmful DNA lesions that can generate chromosomal rearrangements or chromosome losses if not properly repaired. Despite their association with a number of genetic diseases and cancer, the mechanisms by which DSBs cause rearrangements remain unknown. Using a newly developed experimental assay for the analysis of translocations occurring between two chromosomes in Saccharomyces cerevisiae, we found that a single DSB located on one chromosome uses a short homologous sequence found in a third chromosome as a bridge to complete DSB repair, leading to chromosomal translocations. Such translocations are dramatically reduced when the short homologous sequence on the third chromosome is deleted. Translocations rely on homologous recombination (HR) proteins, such as Rad51, Rad52, and Rad59, as well as on the break-induced replication-specific protein Pol32 and on Srs2, but not on Ku70. Our results indicate that a single chromosomal DSB efficiently searches for short homologous sequences throughout the genome for its repair, leading to triparental translocations between heterologous chromosomes. Given the abundance of repetitive DNA in eukaryotic genomes, the results of this study open the possibility that HR rather than nonhomologous end joining may be a major source of chromosomal translocations.

* Corresponding author. Mailing address: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Av. Américo Vespucio s/n, 41092 Sevilla, Spain. Phone: 34 954 468 372. Fax: 34 954 461 664. E-mail: aguilo{at}us.es

{triangledown} Published ahead of print on 3 August 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, October 2009, p. 5441-5454, Vol. 29, No. 20
0270-7306/09/$08.00+0     doi:10.1128/MCB.00256-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»