Mistakes in the DNA sequence are constantly being repaired, but some repair mechanisms are themselves error-prone. One, called break-induced replication (BIR), is initiated at sites at which both DNA strands are broken, and mimics the process of DNA replication. However, its rate of frameshift mutation — a type of mutation that almost always results in loss of gene function — is up to 2,800 times higher than that of normal replication.

Anna Malkova at Indiana University-Purdue University Indianapolis and her team measured mutation rates during BIR in yeast. They found that errors occurred not just close to the site of the double-stranded break, but also farther down the DNA. Most of the mistakes were generated by DNA polymerase enzymes, which replicate DNA and are generally thought to be accurate. The authors say that one of the factors leading to the high mutation rate was elevated levels of nucleotides and that BIR could be an important source of the mutations that drive cancer and evolution.

PLoS Biol. 9, e1000594 (2011)