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AliasesRAD51C, BROVCA3, FANCO, R51H3, RAD51L2, RAD51 paralog C
External IDsOMIM: 602774 MGI: 2150020 HomoloGene: 14238 GeneCards: RAD51C
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for RAD51C
Genomic location for RAD51C
Band17q22Start58,692,573 bp[1]
End58,735,611 bp[1]
RNA expression pattern
PBB GE RAD51C 206066 s at fs.png

PBB GE RAD51C 209849 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 17: 58.69 – 58.74 MbChr 11: 87.38 – 87.4 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

RAD51 homolog C (S. cerevisiae), also known as RAD51C, is a protein which in humans is encoded by the RAD51C gene.[5][6]


The RAD51C protein is one of five paralogs of RAD51, including RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 and XRCC3. They each share about 25% amino acid sequence identity with RAD51 and each other.[7]

The RAD51 paralogs are all required for efficient DNA double-strand break repair by homologous recombination and depletion of any paralog results in significant decreases in homologous recombination frequency.[8]

RAD51C forms two distinct complexes with other related paralogs: BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2) and CX3 (RAD51C-XRCC3). These two complexes act at two different stages of homologous recombinational DNA repair. The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.[8] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament.

The CX3 complex acts downstream of RAD51 recruitment to damage sites.[8] The CX3 complex was shown to associate with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts.[8]

The RAD51C gene is one of genes four localized to a region of chromosome 17q23 where amplification occurs frequently in breast tumors.[9] Overexpression of the four genes during amplification has been observed and suggests a possible role in tumor progression. Alternative splicing has been observed for this gene and two variants encoding different isoforms have been identified.[5]

Clinical significance[edit]

A characteristic of many cancer cells is that parts of some genes contained within these cells have been recombined with other genes. One such gene fusion that has been identified in a MCF-7 breast cancer cell line is a chimera between the RAD51C and ATXN7 genes.[10][11] Since the RAD51C protein is involved in repairing double strand chromosome breaks, this chromosomal rearrangement could be responsible for the other rearrangements.[11]

Mutation, splicing, and epigenetic deficiency in cancer[edit]

RAD51C mutation increases the risk for breast and ovarian cancer, and was first established as a human cancer susceptibility gene in 2010.[12][13][14] Carriers of an RAD51C mutation had a 5.2-fold increased risk of ovarian cancer, indicating that RAD51C is a moderate ovarian cancer susceptibility gene.[15] A pathogenic mutation of RAD51C was present in approximately 1% to 3% of unselected ovarian cancers, and among mutation carriers, the lifetime risk of ovarian cancer was approximately 10-15%.[16][17][18][19]

In addition, there are three other causes of RAD51C deficiency that also appear to increase cancer risk. These are alternative splicing, promoter methylation and repression by over-expression of EZH2.

Three alternatively spliced RAD51C transcripts were identified in colorectal cancers. Variant 1 is joined from the 3' end of exon-6 to the 5' end of exon-8, variant 2 is joined at the 3' end of exon-5 to the 5' end of exon-8, and variant 3 is joined from the 3' end of exon-6 to the 5' end of exon-9.[20] Presence and mRNA expression of variant 1 RAD51C was found in 47% of colorectal cancers. Variant 1 mRNA was expressed about 5-fold more frequently in colorectal tumors than in non-tumor tissues, and when present, was expressed 8-fold more frequently than wild-type RAD51C mRNA. The authors concluded that variant 1 mRNA was associated with the malignant phenotype of colorectal cancers[20]

In the case of gastric cancer, reduced expression of RAD51C was found in about 40% to 50% of tumors, and almost all tumors with reduced RAD51C expression had methylation of the RAD51C promoter.[21] On the other hand, methylation of the RAD51C promoter was only found in about 1.5% of ovarian cancer cases.[17]

EZH2 protein is up-regulated in numerous cancers.[22][23] EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% to 75% of breast cancers have over-expressed EZH2 protein.[24] EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates epigenetic gene silencing of target genes via local chromatin reorganization.[23] EZH2 targets RAD51C, reducing RAD51C mRNA and protein expression (and also represses other RAD51 paralogs RAD51B, RAD51D, XRCC2 and XRCC3).[25] Increased expression of EZH2, leading to repression of RAD51 paralogs and consequent reduced homologous recombinational repair, was proposed as a cause of breast cancer.[26]


RAD51C has been shown to interact with:


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108384 - Ensembl, May 2017
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Further reading[edit]