DNA mutations-long known to fuel cancer as well as evolutionary changes in a living organism-had been thought to be rare events that occur randomly throughout the genome.
Recent studies have shown that cancer development frequently involves the formation of multiple mutations that arise simultaneously and in close proximity to each other. The formation of clustered mutations may result from the process of DNA repair.
Anna Malkova, associate professor of biology in the UI College of Liberal Arts and Sciences, notes that the DNA repair pathway, known as break-induced replication, can promote clusters of DNA mutations.
“Previously, we have shown that double-strand DNA breaks, which can result from oxidation, ionizing radiation and replication errors, can be repaired by BIR,” says Malkova.
“During BIR, one broken DNA end is paired with an identical DNA sequence on another chromosome and initiates an unusual type of replication, which proceeds as a migrating bubble and is associated with the accumulation of large amounts of single-strand DNA,” she says.
Importantly, say the researchers, the paper provides a mechanism to potentially explain how genetic changes form in human cancers.