Homologous recombination repair pathway (HRR)

The homologous recombination repair pathway is a multi-protein, high-fidelity cellular mechanism responsible for the repair of DNA double-strand breaks and interstrand crosslinks using sister chromatids or homologous DNA as templates to ensure error-free restoration. Core proteins include recombinases such as RAD51, tumor suppressors BRCA1 and BRCA2, and other DNA damage response factors. HRR is tightly regulated during the cell cycle and is essential for the maintenance of genomic stability, supporting both DNA replication and damage response. Deficiency of this pathway, most notably due to hereditary or acquired mutations in core HRR genes (e.g., BRCA1/2), leads to increased risk for several cancers and underlies the mechanism of action for PARP inhibitors and platinum-based chemotherapies. While HRR itself is not a direct drug target, components of this pathway are among the most critical molecular determinants both for disease risk and therapeutic strategy in cancer

Other names

Homologous recombination repairHomologous recombination (HR)Homologous recombinational repair (HRR)DNA double-strand break repair by homologous recombination

Synthetic lethality through inhibition of complementary DNA repair (PARP inhibitors block repair of single-strand breaks, leading to double-strand breaks that cannot be repaired if HRR is deficient); DNA damage induction (platinum agents induce DSBs and/or interstrand crosslinks, increasing reliance on HRR for survival)