Chromosomal rearrangements play a major role in the evolution of eukaryotic genomes. Genomic aberrations are also a hallmark of many tumors and are associated with a number of hereditary diseases in humans. The presence of repetitive sequences that can adopt non-canonical DNA structures is one of the factors which can predispose chromosomal regions where they reside to instability. Palindromic sequences (inverted repeats with or without a unique sequence between them) that can adopt hairpin or cruciform structures are frequently found in regions that are prone for gross chromosomal rearrangements (GCRs) in somatic and germ cells in different organisms. Direct physical evidence was obtained that double-strand breaks (DSBs) occur at the location of long inverted repeats, a triggering event for the genomic instability. However, the mechanisms by which palindromic sequences lead to chromosomal fragility are largely unknown. The overall goal of this research is to elucidate the mechanisms of DSB and GCR generation by palindromic sequences in yeast, Saccharomyces cerevisiae.