Short Inverted Repeats Are Hotspots for Genetic Instability: Relevance to Cancer Genomes.

ABSTRACT: Analyses of chromosomal aberrations in human genetic disorders have revealed that inverted repeat sequences (IRs) often co-localize with endogenous chromosomal instability and breakage hotspots. Approximately 80% of all IRs in the human genome are short (<100 bp), yet the mutagenic potential of such short cruciform-forming sequences has not been characterized. Here, we find that short IRs are enriched at translocation breakpoints in human cancer and stimulate the formation of DNA double-strand breaks (DSBs) and deletions in mammalian and yeast cells. We provide evidence for replication-related mechanisms of IR-induced genetic instability and a novel XPF cleavage-based mechanism independent of DNA replication. These discoveries implicate short IRs as endogenous sources of DNA breakage invol

SUBMITTER: Lu S 

PROVIDER: S-EPMC6013304 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature