Mitotic cells are procrastinators—at least when it comes to making repairs. As Giunta et al. report, the cells label broken DNA, waiting until after mitosis to fix it.
Triggered by radiation and certain chemicals, double-strand breaks (DSBs) are the most dangerous type of chromosome damage. They can lead to genomic instability that promotes cancer. A DSB triggers a complex series of molecular responses that eventually mends the DNA. But what if the DNA fractures during mitosis? Researchers have found that if the damage occurs early enough—up to the middle of prophase—a cell can slow or even halt mitosis to make repairs. After that, however, mitosis is unstoppable.
Giunta et al. discovered that cells don't ignore these late breaks. Instead, they fire up the DNA damage response, allowing early events such as the phosphorylation of the H2AX histone, which labels the site of the break. The process then ceases. Later events in the cascade, including the arrival of ubiquitin-adding proteins such as BRCA1, don't occur during mitosis.
Cells fix the breaks during the following interphase, the researchers found. The work suggests that during mitosis cells mark the sites of damage rather than actually patching up the DNA. But this step is crucial. If mitotic cells can't perform the early stages of DSB repair, they are more likely to die from radiation exposure, Giunta et al. showed. Why don't cells simply finish the job during mitosis? The answer isn't clear. The DNA might be too tightly condensed for repair proteins to gain access to the breaks, or these proteins might be inactive.
