Homologous recombination and non-homologous end joining double-strand break repair machinery (HR and NHEJ DSB repair machinery)

The homologous recombination (HR) and non-homologous end joining (NHEJ) double-strand break repair machinery comprises the essential protein complexes responsible for maintaining genomic integrity following DNA damage. HR is a high-fidelity repair pathway that utilizes a homologous DNA template, typically a sister chromatid, and is active primarily during the S and G2 phases of the cell cycle (Source: Nature Reviews Molecular Cell Biology, 2019). NHEJ, conversely, is a faster but more error-prone process that directly ligates DNA ends without a template and operates throughout the cell cycle (Source: NIH/NCBI, 2021). Deficiencies in these pathways, particularly HR, are strongly associated with an increased risk of cancers, including breast and ovarian malignancies linked to BRCA1/2 mutations. Pharmacological intervention often targets these pathways to induce synthetic lethality, as seen with PARP inhibitors in HR-deficient tumors, or to enhance the efficacy of DNA-damaging agents like radiation and chemotherapy by inhibiting key components such as DNA-PKcs or ATM (Source: Journal of Clinical Oncology, 2020; PubMed, 2022).

Other names

DNA double-strand break repair (DSBR) pathwaysHR/NHEJ pathwaysDNA damage response (DDR) machinery

Synthetic lethality via PARP inhibition in cells with homologous recombination deficiency (HRD); direct inhibition of DNA-PKcs or ATM to block non-homologous end joining (NHEJ) or HR-mediated repair, sensitizing cells to DNA-damaging agents.