Ruiz JF, et al. (2009) Chromosomal translocations caused by either pol32-dependent or pol32-independent triparental break-induced replication. Mol Cell Biol 29(20):5441-54
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 S. 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 (BIR)-specific protein Pol32 and 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, this study opens the possibility that HR rather than Non-Homologous End Joining (NHEJ) may be a major source for chromosomal translocations.
|Status: Published||Type: Journal Article||PubMed ID: 19651902|
Topics addressed in this paper
Number of different genes curated to this paper: 9
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