Homologous Recombination Repair In Breast Cancer: Computational Strategies To Inhibit RAD51C Function

Abstract

RAD51C is essential in the homologous recombination (HR)^[1] pathway for repairing DNA double-strand breaks (DSBs)^[2]. It coordinates with BRAC2^[3] and FANCD2 ^[3]to facilitate RAD51 loading and strand invasion during repair. Mutations in RAD51C ^[4]impair this process, leading to genomic instability and promoting tumorigenesis in tissues like breast and ovary. To identify potential Rad51C inhibitors, computational drug discovery approaches such as molecular docking, and virtual screening are employed. These techniques verifies 3D structure of RAD51C’s to predict binding affinities of small molecules, helping to screen thousands of compounds efficiently. Coupled with in silico ADMET profiling, this pipeline accelerates the discovery of selective inhibitors that may enhance sensitivity to DNA-damaging therapies or PARP inhibitors in RAD51C deficient cancers.