Thomas Hollis, Ph.D.
The maintenance of DNA integrity is essential for normal cellular function and for the propagation of the genetic code to successive generations. A variety of endogenous cellular reagents and exogenous toxins are capable of reacting with and modifying DNA. These modifications can pose blocks to replicative DNA polymerases and/or interfere with the binding of regulatory proteins to DNA causing wide spread cellular responses. Repair of lesions in DNA is a critical cellular response mediated by enzymes that can accurately detect, remove and/or correct the damaged bases.
Research in my laboratory focuses on the structural biology of proteins involved in DNA repair. We use a combination of X-ray crystallography, biochemistry and molecular biology to address questions of DNA damage recognition and repair by proteins.
In collaboration with the Perrino Laboratory we are determining the X-ray crystal structures of the 3’-5’ DNA exonucleases TREX1 and TREX2. Our goal is to understand how the dimeric structure of these proteins contributes to their substrate specificity and catalytic activity.
Additionally, we are working on determining the structures and functions of proteins involved in the cancer susceptibility syndrome, Fanconi anemia. This rare disease is a result of the cell’s inability to recognize or repair certain types of DNA damage, particularly interstrand crosslinks.