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Watching homologous recombination one molecule at a time

Research Scholar

Gayan Senavirathne, assistant lecturer, University of Colombo (Sri Lanka)
Richard Fishel, faculty mentor

Background

  • Hometown: Panadura, Sri Lanka
  • Degrees received: PhD in chemistry, Wayne State Univerisity, Detroit, Michigan, United States.

What is the issue or problem addresses in your research?

Double-strand breaks (DSBs) occur ubiquitously as a result of external and internal assaults on genomic DNA. Homologous recombination (HR) is required for faithful repairing of DSBs. Unrepaired DSBs are one of the most genotoxic lesions and can lead to gross chromosomal rearrangements, a clear hallmark of cancer. Although the general mechanism of HR is known, the molecular details of some of the important steps are not well understood. This research is focused on dissecting HR using in vitro biochemical experiments.

What methodology did you use in your research?

We use in vitro biochemical experiments including cutting-edge high throughput single-molecule imaging. This is accomplished by generating all the necessary HR enzymes such as HsRAD51, HsRPA, HsRAd54 and specific DNA substrates such as mononucleosomes.

What are the purpose/rationale and implications of your research?

Unique single-molecule tools developed in this research can be extended not only to elucidate mechanistic details, but also to characterize cancer/disease-related mutations of HR proteins. Our experimental approach creates a platform to quantitatively and visually evaluate the biophysical properties of these defects. Comparison of the functional consequences of novel HR mutations with well-known cancer-related mutations will provide a foundation for making predictions.