Revealing New Mechanisms of Exposure-Induced Homologous Recombination

We have found that a single acute exposure to a cancer chemotherapeutic induces recombination in distantly descendant cells and in their neighbors.

In our studies of conditions that stimulate homologous recombination, we learned that recombination events are not only directly induced by exposure to DNA damaging agents, but they can be induced through two other interesting mechanisms: persistent effects and bystander effects. Persistent genomic instability is defined as a persistently increased risk of de novo mutations, or in this case, recombination events. Bystander effects describe a situation in which a cell that has been exposed to a DNA damaging agent can induce DNA damage in a neighboring unexposed cell. It has long been known that radiation induces both persistent and bystander effects. In this laboratory, we have shown that exposure to chemical used during chemotherpay induces both persisten and bystander effects,, thus demonstrating that these effects are not exclusive to radiation, but rather are likely to be a more general response. Furthermore, we have shown that these two responses are related: cells that have a persistent instability phenotype can induce a bystander effect in neighboring undamaged cells.