In order to accurately replicate and pass on their genetic material, cells must repair DNA damage as it arises. One of the most dangerous types of DNA damage is the double-strand break. Failure to repair double-strand breaks can result in cell death by apoptosis, while inaccurate repair can be mutagenic. The importance of double-strand break repair has been highlighted by the identification of many inherited human diseases that are caused by mutation of genes involved in the repair process.

Normal metaphase chromosome spread from female neuroblast	Metaphase chromosome spread from female neuroblast exposed to 1000 rads of gamma irradiation. Chromosome breaks and translocations can be readily observed

Double-strand breaks can be repaired by two main classes of pathways: non-homologous end-joining and homologous recombination. End-joining entails processing of broken ends and subsequent ligation and is often error-prone (it can be thought of as the "duct tape" approach to repair). Homologous recombination involves using a homologous template for repair and is generally error-free. Different cell types employ these pathways (or combinations of them) to different extents during development, depending on cell cycle and developmental cues.

Our laboratory is using Drosophila melanogaster as a model system to:

1. Investigate how and when these double-strand break repair pathways are used in different cell types and
2. Characterize genes that play crucial roles in each pathway.

Our research employs a variety of classical and molecular genetic approaches, including powerful assays in which we can create double-strand breaks at known sites in the genome and recover and molecularly analyze repair events. Our long-term goal is to elucidate the mechanisms by which cells "choose" the appropriate pathways to repair different types of DNA breaks.

Male fly in which P-element induced double-strand breaks in eye progenitor cells are being repaired by homologous recombination (red patches) and non-homologous end-joining (yellow patches).

Current projects in the lab include:

1. Using an inducible I-SceI endonuclease system to determine the extent that various repair pathways are utilized in different tissues and developmental stages.
2. Determining the genetic components of alternative end-joining repair pathways.
3. Investigating potential roles of error-prone DNA polymerases in DNA double-strand break repair.
4. Identifying proteins and pathways that repair camptothecin-induced damage.
5. Developing techniques for targeted mutagenesis using transposable elements and zinc finger nucleases.

This material is based upon work supported by the National Science Foundation under Grant No. 0643253. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation