Homologous recombination/repair (HR) is an essential process for maintaining the integrity of the genome. HR mediates the repair of DNA damage and is also responsible for the repair of stalled replication forks, meiotic recombination events and telomere maintenance. Therefore, it is logical that disruption of HR is associated with an accumulation of DNA damage and resultant chromosomal instability. If not corrected, DNA damage can potentially compound as cells proliferate and replicate the genomic errors creating numerous health risks including cancer.
Tumor suppressor protein, breast cancer susceptibility protein 2, (BRCA2) functions in the loading of the recombinase enzyme, Rad51, to damaged DNA. Mutant versions of this protein are associated with an increased risk of several types of cancer. Interestingly, RAD52, an essential recombinatory protein in the eukaryotic model organism Saccharomyces cerevisiae, seems to have little to no function in healthy mammalian cells where BRCA2 is present. However, synthetic lethality is induced in cells where RAD52 is deficient in combination with BRCA2. Therefore, development of a RAD52 inhibitor may induce synthetic lethality specifically in cancer cells where a BRCA2 deficiency is present while leaving healthy cells unaffected.
Unfortunately, crystallization of the complete protein has been unachievable due to a disordered C-terminus that prevents it from conforming to a single structure. This presentation will expand on the development of strategic RAD52 truncations to minimize the disordered characteristic of the protein to gain insight into the structure of RAD52.
David Fischer ’14
De Pere, WI
Major: Biochemistry and Molecular Biology
Sponsor: Craig Tepper