Alternative titles; symbols
HGNC Approved Gene Symbol: RAD51AP1
Cytogenetic location: 12p13.32 Genomic coordinates (GRCh38) : 12:4,538,890-4,560,047 (from NCBI)
RAD51 (179617), a eukaryotic homolog of the bacterial RecA recombinase, plays a role in a variety of recombination events in the eukaryotic cell. Using a yeast 2-hybrid screen with human RAD51 as the bait, Mizuta et al. (1997) isolated mouse cDNAs corresponding to a gene that they designated Rab22. The Rab22 protein interacted with RAD51 in vitro and colocalized with RAD51 in large nuclear foci in hamster cells. Kovalenko et al. (1997) also used a yeast 2-hybrid screen with RAD51 as the bait and isolated a HeLa cell cDNA encoding a protein that they called PIR51 for 'protein interacting with Rad51'. The predicted PIR51 protein has 335 amino acids and a calculated pI of 9.95. The authors suggested that PIR51 is the human homolog of mouse Rab22 since the 2 proteins share 63% sequence identity. Northern blot analysis revealed that PIR51 is expressed as a 2.4-kb mRNA in human testis and thymus, and at lower levels, in colon and small intestine.
Kovalenko et al. (1997) found that recombinant PIR51 bound RNA and single- and double-stranded DNA, and was capable of aggregating DNA. They suggested that PIR51 may represent a novel member of the multiprotein complexes thought to carry out homologous recombination and DNA repair in mammalian cells.
Modesti et al. (2007) found that RAD51AP1 specifically stimulated joint molecule formation through structure-specific DNA binding and physical contact with RAD51. RAD51AP1 was required to protect HeLa cells from agents that cause DNA double-strand breaks. At the biochemical level, RAD51AP1 had selective affinity for branched DNA structures, and it stimulated D loop formation by RAD51, a pivotal step in recombination. Modesti et al. (2007) concluded that the affinity of RAD51AP1 for the central protein and DNA intermediates of recombination confers on it the ability to preserve genome integrity.
Wiese et al. (2007) found that purified RAD51AP1 bound both double-stranded DNA and a D loop structure and that it stimulated the RAD51-mediated D-loop reaction. Biochemical and cytologic experiments showed that RAD51AP1 functioned at a step subsequent to the assembly of the RAD51-single-stranded DNA nucleoprotein filament.
By analysis of an interspecific backcross, Mizuta et al. (1997) mapped the Rab22 gene to the distal region of mouse chromosome 6. Using fluorescence in situ hybridization, Kovalenko et al. (1997) mapped the PIR51 gene to chromosome 12p13.2-p13.1, a region that shows homology of synteny with the mouse chromosome 6 segment containing the Rab22 gene.
Kovalenko, O. V., Golub, E. I., Bray-Ward, P., Ward, D. C., Radding, C. M. A novel nucleic acid-binding protein that interacts with human Rad51 recombinase. Nucleic Acids Res. 25: 4946-4953, 1997. [PubMed: 9396801] [Full Text: https://doi.org/10.1093/nar/25.24.4946]
Mizuta, R., LaSalle, J. M., Cheng, H.-L., Shinohara, A., Ogawa, H., Copeland, N., Jenkins, N. A., Lalande, M., Alt, F. W. RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51 protein. Proc. Nat. Acad. Sci. 94: 6927-6932, 1997. [PubMed: 9192668] [Full Text: https://doi.org/10.1073/pnas.94.13.6927]
Modesti, M., Budzowska, M., Baldeyron, C., Demmers, J. A. A., Ghirlando, R., Kanaar, R. RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination. Molec. Cell 28: 468-481, 2007. [PubMed: 17996710] [Full Text: https://doi.org/10.1016/j.molcel.2007.08.025]
Wiese, C., Dray, E., Groesser, T., San Filippo, J., Shi, I., Collins, D. W., Tsai, M.-S., Williams, G. J., Rydberg, B., Sung, P., Schild, D. Promotion of homologous recombination and genomic stability by RAD51AP1 via RAD51 recombinase enhancement. Molec. Cell 28: 482-490, 2007. [PubMed: 17996711] [Full Text: https://doi.org/10.1016/j.molcel.2007.08.027]