DNA damage is a constant challenge to cells and a primary event leading to cancer. Double-strand breaks – when both strands of the double helix are severed – is among the most lethal forms of damage; it is essential that such breaks be repaired efficiently and with high fidelity. We seek to understand the molecular mechanisms through which this is achieved. We use primarily genetic approaches (classical and molecular, forward and reverse), using the fruit fly Drosophila melanogaster as a model organism.
Double-strand breaks occur spontaneously due to problems during DNA replication, or they can be induced by exposure to ionizing radiation or clastogenic chemicals. Meiotic cells actually induce programmed double-strand breaks. The goal of meiosis is to generate haploid gametes from a diploid cell. To do this, homologous chromosomes must pair and stick together until anaphase of meiosis I. How do they stick together? By making crossovers. The pathway for generating crossovers begins with the formation of double-strand breaks. These breaks are repaired in a highly regulated way to ensure that crossovers are generated in the right places, but not in the wrong places. We are interested in the molecular mechanisms of this specialized repair process and how it differs from double-strand break repair in non-meiotic cells.
These projects are discussed in more detail on our lab web site.