CCAR2, also known as DBC1 (deleted in breast cancer 1), is a multifaceted protein involved in diverse physiological and pathophysiological processes [2,4]. It acts as a coregulator of various transcription factors and a critical regulator of numerous epigenetic modifiers, playing roles in apoptosis, DNA repair, metabolism, and tumorigenesis [2]. It is part of the 53BP1-RIF1 pathway which restricts DNA double-strand break (DSB) resection and promotes non-homologous end joining (NHEJ) repair [1].

Gene knockout studies have provided significant insights into CCAR2 functions. In a BRCA1-deficient cell line, knockout of CCAR2 led to elevated DSB end-resection, RAD51 loading, and PARP inhibitor (PARPi) resistance, indicating its role in suppressing homologous recombination [1]. CCAR2-deficient cells also showed defects in cell division, with perturbed mitotic phase, premature loss of centromere cohesion, and activation of the abscission checkpoint, suggesting it governs mitotic events to maintain chromosomal stability [3]. In osteosarcoma cells, silencing CCAR2 prevented the malignant phenotype both in vitro and in nude mice [5].

In conclusion, CCAR2 plays essential roles in DNA repair, cell cycle regulation, and cancer-related processes. Gene knockout models have been crucial in revealing its functions, especially in understanding DNA repair mechanisms and cancer-associated phenotypes such as in osteosarcoma, providing potential targets for therapeutic interventions [1,3,5].