![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
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.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://mcb.asm.org/ .
ACKNOWLEDGMENTS
This work was funded by grants from the Spanish Ministry of Research and Innovation (BFU2006-05260 and CDS2007-0015) and Junta de Andalucia (CVI-624 and BIO-102). J.F.R. and B.G.-G. were the recipients of postdoctoral and predoctoral grants, respectively, from the Spanish Ministry of Science and Education.
We thank H. Klein, J. Haber, and A. Gabriel for providing yeast strains and plasmids and B. Pardo for helpful discussions and critical reading of the manuscript.