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HGNC Approved Gene Symbol: RAD51B
Cytogenetic location: 14q24.1 Genomic coordinates (GRCh38): 14:67,819,779-68,683,096 (from NCBI)
Members of the RAD51 (179617) family, including RAD51L1, function in both mitotic and meiotic homologous recombination and in DNA double-strand break repair.
By computerized searching of an EST database, Albala et al. (1997) identified human and mouse cDNAs encoding a protein with homology to RAD51. The predicted 350-amino acid human protein, designated RAD51B by them, shares 27 to 30% sequence identity with yeast and chicken RAD51 and human RAD51A. RAD51B contains conserved nucleotide-binding motifs, suggesting that it is an ATPase. Northern blot analysis revealed that RAD51B was expressed as a 1.8-kb mRNA in all tissues examined. In both mouse and human, the highest levels of expression were seen in testis, thymus, ovary, and spleen, tissues that undergo recombination events.
Rice et al. (1997) also isolated human and mouse cDNAs encoding RAD51B, which they called REC2. They reported that the sequences of the human and mouse proteins are 84% identical. By RT-PCR, Rice et al. (1997) found that RAD51B expression was undetectable in cultured cells unless the cells were treated with ionizing radiation.
Cartwright et al. (1998) isolated an alternatively spliced RAD51B, or R51H2, cDNA that differed from that reported by Rice et al. (1997) at the 3-prime end. They determined that both forms are found in cDNA libraries from various tissues.
Masson et al. (2001) found that antibody directed against RAD51L3 (602954) immunoprecipitated a complex from HeLa cell lysates that included RAD51L1, XRCC2 (600375), and RAD51C (602774), along with RAD51L3. Interactions between these proteins were confirmed in pull-down assays using recombinant proteins expressed in sf9 insect cells. Gel filtration of the complex indicated an apparent molecular mass of about 180 kD, suggesting a 1:1:1:1 stoichiometry of the 4 subunits. Binding assays, confirmed by electron microscopic visualization, indicated that the purified complex binds single-stranded or nicked DNA. This binding was found to be dependent on Mg(2+) but independent of ATP. DNA-stimulated ATPase activity of the complex was extremely low. Masson et al. (2001) also identified a second, heterodimeric protein complex between RAD51C and XRCC3 (600675). Using coprecipitation and multiple pull-down assays, Liu et al. (2002) confirmed interaction between the same RAD51 paralogs in the same 2 distinct protein complexes.
Adelman et al. (2013) reported that Helq (606769) helicase-deficient mice exhibit subfertility, germ cell attrition, interstrand crosslink (ICL) sensitivity, and tumor predisposition, with Helq heterozygous mice exhibiting a similar, albeit less severe, phenotype than the null, indicative of haploinsufficiency. Adelman et al. (2013) established that HELQ interacts directly with the RAD51 (179617) paralog complex BCDX2 (RAD51B, RAD51C, RAD51D, 602954; and XRCC2) and functions in parallel to the Fanconi anemia pathway to promote efficient homologous recombination at damaged replication forks. Adelman et al. (2013) concluded that their results revealed a critical role for HELQ in replication-coupled DNA repair, germ cell maintenance, and tumor suppression in mammals.
By analysis of a somatic cell hybrid panel, fluorescence in situ hybridization, and inclusion within YACs, Albala et al. (1997) mapped the RAD51B gene to 14q23-q24.2. Rice et al. (1997) refined the map position to 14q23.3-q24.1 using fluorescence in situ hybridization and analysis of a radiation hybrid panel.
Associations Pending Confirmation
Orr et al. (2012) conducted a genomewide association study of male breast cancer (see 114480) comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (rs1314913, p = 3.02 x 10(-13); odds ratio = 1.57, 95% confidence interval 1.39-1.77).
For discussion of a possible association between variation near the RAD51B gene and age-related macular degeneration, see ARMD1 (603075).
The high mobility group protein gene HMGIC (600698) is the chromosome 12q15 translocation partner (target gene) in a variety of benign solid tumors. Schoenmakers et al. (1999) reported that the recombinational repair gene RAD51B on 14q23-q24.2 is the preferential translocation partner of HMGIC in uterine leiomyomas (150699). In histologically benign uterine leiomyomas from 34 patients, Heim et al. (1988) found an apparently identical reciprocal translocation t(12;14)(q14-15;q23-24) in the tumors of 4 patients. A fifth patient showed a t(2;14)(p11;p11). The pathogenetically critical sequences in the RAD51B gene seemed to reside in the last coding exon of a novel RAD51B isoform, which encodes a domain containing a putative transmembrane anchor and was expressed in uterus but not in a wide variety of other tissues tested by Schoenmakers et al. (1999). Consistent chromosomal rearrangements within RAD51B and expression of fusion transcripts were demonstrated, structurally resulting in an allelic knockout of the uterine isoform of RAD51B and confirming a pleiotropic function of this gene.
Adelman, C. A., Lolo, R. L., Birkbak, N. J., Murina, O., Matsuzaki, K., Horejsi, Z., Parmar, K., Borel, V., Skehel, J. M., Stamp, G., D'Andrea, A., Sartori, A. A., Swanton, C., Boulton, S. J. HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis. Nature 502: 381-384, 2013. [PubMed: 24005329] [Full Text: https://doi.org/10.1038/nature12565]
Albala, J. S., Thelen, M. P., Prange, C., Fan, W., Christensen, M., Thompson, L. H., Lennon, G. G. Identification of a novel human RAD51 homolog, RAD51B. Genomics 46: 476-479, 1997. Note: Erratum: Genomics 51: 480 only, 1998. [PubMed: 9441753] [Full Text: https://doi.org/10.1006/geno.1997.5062]
Cartwright, R., Dunn, A. M., Simpson, P. J., Tambini, C. E., Thacker, J. Isolation of novel human and mouse genes of the recA/RAD51 recombination-repair gene family. Nucleic Acids Res. 26: 1653-1659, 1998. [PubMed: 9512535] [Full Text: https://doi.org/10.1093/nar/26.7.1653]
Heim, S., Nilbert, M., Vanni, R., Floderus, U.-M., Mandahl, N., Liedgren, S., Lecca, U., Mitelman, F. A specific translocation, t(12;14)(q14-15;q23-24), characterizes a subgroup of uterine leiomyomas. Cancer Genet. Cytogenet. 32: 13-17, 1988. [PubMed: 3355995] [Full Text: https://doi.org/10.1016/0165-4608(88)90305-6]
Liu, N., Schild, D., Thelen, M. P., Thompson, L. H. Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells. Nucleic Acids Res. 30: 1009-1015, 2002. [PubMed: 11842113] [Full Text: https://doi.org/10.1093/nar/30.4.1009]
Masson, J.-Y., Tarsounas, M. C., Stasiak, A. Z., Stasiak, A., Shah, R., McIlwraith, M. J., Benson, F. E., West, S. C. Identification and purification of two distinct complexes containing the five RAD51 paralogs. Genes Dev. 15: 3296-3307, 2001. [PubMed: 11751635] [Full Text: https://doi.org/10.1101/gad.947001]
Orr, N., Lemnrau, A., Cooke, R., Fletcher, O., Tomczyk, K., Jones, M., Johnson, N., Lord, C. J., Mistopoulos, C., Zvelebil, M., McDade, S. S., Buck, G., and 33 others. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk. Nature Genet. 44: 1182-1184, 2012. [PubMed: 23001122] [Full Text: https://doi.org/10.1038/ng.2417]
Rice, M. C., Smith, S. T., Bullrich, F., Havre, P., Kmiec, E. B. Isolation of human and mouse genes based on homology to REC2, a recombinational repair gene from the fungus Ustilago maydis. Proc. Nat. Acad. Sci. 94: 7417-7422, 1997. [PubMed: 9207106] [Full Text: https://doi.org/10.1073/pnas.94.14.7417]
Schoenmakers, E. F. P. M., Huysmans, C., Van de Ven, W. J. M. Allelic knockout of novel splice variants of human recombination repair gene RAD51B in t(12;14) uterine leiomyomas. Cancer Res. 59: 19-23, 1999. [PubMed: 9892177]