A wide variety of oxidative DNA damage is introduced into nuclear and mitochondrial DNA by reactive oxygen species (ROS). Sources of ROS include cellular metabolism, inflammation and exogenous agents used in the treatment of cancer. If DNA damage is not repaired or is mis-repaired, it can result in mutations, chromosomal aberrations or cell death. In fact DNA damage has been implicated in multistage carcinogenesis and aging. DNA repair is therefore important for the maintenance of genetic integrity and stability, and cell survival. This laboratory works on two projects:

Project A
Radiotherapy introduces clusters of DNA lesions, which can cause incomplete repair and the generation of lethal double-strand breaks. We want to identify repair enzymes that can generate lethal double-strand breaks from radiation DNA damage and determine whether it is possible to manipulate the DNA repair system in a tumor during radiotherapy to enhance tumor cell killing.

Procedures
Cell culture, cloning of DNA into expression vectors, mammalian cell transfection, Southern and northern analysis, PCR, agarose gel and polyacrylamide gel electrophoresis, DNA sequencing, DNA footprinting

Lynn Harrison, Katherine L. Brame, Laura E.Geltz and April M. Landry (2006). Closely opposed apurinic/apyrimidinic sites are converted to double strand breaks in Escherichia coli even in the absence of exonuclease III, endonuclease IV, nucleotide excision repair and AP lyase cleavage. DNA Repair 5, 324-335.

Svitlana Malyarchuk, Douglas Wright, Reneau Castore, Emily Klepper, Bernard Weiss, Aidan Doherty, Lynn Harrison (2007). Expression of Mycobacterium tuberculosis Ku and Ligase D in Escherichia coli results in RecA and RecB-independent DNA end-joining at regions of micro-homology. DNA Repair 6,1413-1424.