RAD51C

RAD51C, also known as RAD51-like 3 and FANCO, is a human gene that encodes a member of the RAD51 family of recombinase proteins. RAD51C participates in homologous recombination and the DNA damage response, contributing to the maintenance of genomic stability after double-strand breaks or replication stress.

In human cells, RAD51C is part of two RAD51 paralog complexes. The BCDX2 complex is composed of RAD51B, RAD51C, RAD51D, and XRCC2, while the CX3 complex consists of RAD51C and XRCC3. These complexes assist RAD51 in filament formation on single-stranded DNA, promote strand pairing and exchange, and help resolve recombination intermediates required for accurate DNA repair. RAD51C also participates in checkpoint signaling and replication fork protection, contributing to overall genome maintenance. The protein is primarily localized to the nucleus and is regulated through the cell cycle.

RAD51C interacts with other key repair factors, including BRCA2 and PALB2, linking homologous recombination to broader DNA damage response pathways. Its activity is important for the efficiency and fidelity of repair of double-strand breaks and for protecting stalled replication forks.

Clinical significance: Germline pathogenic variants in RAD51C are associated with an increased risk of breast and ovarian cancers. Heterozygous mutations confer susceptibility, while biallelic mutations can cause Fanconi anemia-like syndromes, sometimes referred to as FANCO-related disorders.

The gene is evolutionarily conserved in eukaryotes and is studied in various model systems to elucidate its precise roles in homologous recombination and cancer predisposition.