Summary
This project aims to investigate the function of the APE2 nuclease in alternative end-joining (Alt-EJ) DNA repair, particularly in HR-deficient cancer cells, to develop new therapeutic strategies against PARP inhibitor resistance.
Deciphering the function of the APE2 nuclease during repair by alternative end-joining and its role in HR-deficient cells
US · IL
NIH
grant
awarded
#nih-5R01CA266100-04
What they want
The research involves two main aims: 1) molecular characterization of APE2's function and mechanism in Alt-EJ, including its specific role, involved domains and biochemical activities, and mechanism of recruitment to DNA double-strand breaks (DSBs); and 2) uncovering the therapeutic potential of APE2 inhibition in HR-deficient cancer cells by identifying the repair function driving its synthetic lethality with HR and determining its synergy with PARP inhibitors to prevent or overcome resistance.
Deliverables
- Improved fundamental understanding of the Alt-EJ repair pathway
- Sufficient knowledge on APE2 to enable future development of an inhibitor
- Identification of APE2's repair function that drives its synthetic lethality with HR
- Determination of APE2 inhibition's potential to synergize with PARP inhibitors and overcome resistance
Technical requirements
- Genome-wide CRISPR/Cas9 screens
- Alt-EJ assays based on repair reporters
- Alt-EJ-mediated fusion of telomeres
Risks & flags
Incumbent: The proposing lab/researcher
- This appears to be a summary of a specific research project or grant application from a particular lab, not an open procurement opportunity for external bidders.
