Genomic instability and repair mediated by common repeated sequences

Abstract

If you happen to find a suspicious cell, say, in your soup, you may recognize to what species it belongs simply by looking at its chromosome configuration (karyotype) under the microscope. This approach works because most cells of most organisms have a stable genome, and gross chromosomal rearrangements (GCRs) such as translocations, inversions, and deletions of big chunks of chromosomes are relatively rare. This is in stark contrast to cancer cells, which exhibit abundant GCRs (1). When the borders of such rearrangements are mapped, they often belong to repetitive sequences, which are scattered across the genome of all organisms. Tandem repetitive sequences are also present at the ends of the eukaryotic chromosomes, forming the telomeres, which help replicate the genome and protect it from degradation (2). Interestingly, telomeric repeats can also be found at internal positions along the chromosomes in many organisms. These interstitial telomeric sequences (ITSs) often colocalize with chromosomal fragile sites and with endpoints of GCRs (3, 4). However, little is known about the mechanisms responsible for genome instability at interstitial telomeric sequences. In PNAS, Aksenova et al. (5) present a study in which the power of yeast genetics is harnessed to address this particular question. Using a sophisticated genetic trap, the authors measure the rate of GCR formation and characterize the molecular mechanisms leading to them. The results show a surprisingly high level of recombinational activity involving these repeated sequences.