The mechanisms governing non-recurrent human structural variation (SV) are diverse and often poorly understood. I am investigating how human DNA maintains fidelity in the context of a repetitive genome. Human Alu elements number over one million copies per human genome, and recent studies have found that these repeat sequences often mediate SVs in some loci. Through computational, molecular biological and genomic techniques, we will identify regions susceptible to this form of SV and investigate the enzymes that limit or promote Alu-mediated rearrangements. These lines of inquiry could find regions prone to instability in human cancers and lead to targets for therapy.