Alternative titles; symbols
HGNC Approved Gene Symbol: TSN
Cytogenetic location: 2q14.3 Genomic coordinates (GRCh38): 2:121,755,651-121,767,853 (from NCBI)
Kasai et al. (1994) identified a protein they termed recombination hotspot-associated factor (RcHF1), which specifically binds to the signal-like sequences at the breakpoint junction of 8q24 and 1p32 in acute lymphoblastic leukemia (ALL) patients carrying t(8;14)(q24;q11) and t(1;14)(p32;q11) translocations involving the TCR delta-chain locus (TCRD; see 186810). Aoki et al. (1994) showed that an analogous protein, which they designated BCLF1, specifically binds to a target sequence within the clustered breakpoint region of the BCL2 oncogene (151430) in follicular lymphoma patients carrying t(14;18)(q32;q21) translocations. It was proposed that these binding activities at recombination hotspot regions may play a crucial role in chromosomal translocations in lymphoid neoplasms. Aoki et al. (1995) purified the BCLF1 protein to homogeneity and determined that it is identical to RcHF1. Molecular gene cloning experiments revealed that the purified protein, which they named translin (TSN), is a previously undescribed DNA-binding protein with no significant similarity to known proteins. (The designation 'translin' came from selected letters in 'translocation.') In addition, Aoki et al. (1995) found that nuclear localization of translin was limited to lymphoid cell lines with rearranged Ig and processes such as DNA repair, replication, or recombination. In their native form, translin polypeptides form a multimeric structure that is responsible for its DNA binding activity.
Aoki et al. (1997) found that the human and mouse translin genes have identical genomic structures with 6 exons and a GC-rich upstream region.
Badge et al. (2000) studied a subtelomeric region at 16p13.3 that displays a 300-fold increase in crossovers compared to the genomic average rate. Segregation analysis of CEPH and other pedigrees yielded 6 paternal crossover breakpoints in the approximately 85-kb interval between the minisatellite loci D16S309 (MS205) and D16S83 (EKMDA2). Three crossovers were mapped to within the same small (less than 3 kb) interval, which did not colocalize with any tandem repeat array or expressed sequence. Sequence analysis revealed the presence of recombination-associated motifs and binding sites for translin. The authors concluded that this locus represents an intense male-specific recombination hotspot.
Hosaka et al. (2000) demonstrated that the presence of the translin binding motif may be one of the important determinants for the location of breakpoints in the TLS (137070) and CHOP (126337) genes which are fused by translocation t(12;16) in liposarcomas.
Liu et al. (2009) reconstituted long double-stranded RNA- and duplex siRNA-initiated RNA-induced silencing complex (RISC) activities with the use of recombinant Drosophila Dicer-2 (see 606241), R2D2, and Ago2 (606229) proteins. They used this core reconstitution system to purify an RNAi regulator that they termed C3PO (component 3 promoter of RISC), a complex of translin and TRAX (602964). C3PO is a magnesium ion-dependent endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products. Liu et al. (2009) showed that TRAX is unstable without translin and that TRAX is the catalytic subunit of C3PO. Liu et al. (2009) concluded that their study established an in vitro RNAi reconstitution system and identified C3PO as a key activator of the core RNAi machinery.
By in situ hybridization and analysis of somatic cell hybrids, Aoki et al. (1997) mapped the human TSN gene to 2q21.1.
Aoki, K., Inazawa, J., Takahashi, T., Nakahara, K., Kasai, M. Genomic structure and chromosomal localization of the gene encoding translin, a recombination hotspot binding protein. Genomics 43: 237-241, 1997. [PubMed: 9244443] [Full Text: https://doi.org/10.1006/geno.1997.4796]
Aoki, K., Nakahara, K., Ikegawa, C., Seto, M., Takahashi, T., Minowada, J., Strominger, J. L., Maziarz, R. T., Kasai, M. Nuclear proteins binding to a novel target sequence within the recombination hotspot regions of Bcl-2 and the immunoglobulin D(H) gene family. Oncogene 9: 1109-1115, 1994. [PubMed: 8134113]
Aoki, K., Suzuki, K., Sugano, T., Tasaka, T., Nakahara, K., Kuge, O., Omori, A., Kasai, M. A novel gene, 'Translin,' encodes a recombination hotspot binding protein associated with chromosomal translocations. Nature Genet. 10: 167-174, 1995. [PubMed: 7663511] [Full Text: https://doi.org/10.1038/ng0695-167]
Badge, R. M., Yardley, J., Jeffreys, A. J., Armour, J. A. L. Crossover breakpoint mapping identifies a subtelomeric hotspot for male meiotic recombination. Hum. Molec. Genet. 9: 1239-1244, 2000. [PubMed: 10767349] [Full Text: https://doi.org/10.1093/hmg/9.8.1239]
Hosaka, T., Kanoe, H., Nakayama, T., Murakami, H., Yamamoto, H., Nakamata, T., Tsuboyama, T., Oka, M., Kasai, M., Sasaki, M. S., Nakamura, T., Toguchida, J. Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;16). Oncogene 19: 5821-5825, 2000. [PubMed: 11126370] [Full Text: https://doi.org/10.1038/sj.onc.1203943]
Kasai, M., Aoki, K., Matsuo, Y., Minowada, J., Maziarz, R. T., Strominger, J. L. Recombination hotspot associated factors specifically recognize novel target sequences at the site of interchromosomal rearrangements in T-ALL patients with t(8;14)(q24;q11) and t(1;14)(p32;q11). Int. Immun. 6: 1017-1025, 1994. [PubMed: 7947454] [Full Text: https://doi.org/10.1093/intimm/6.7.1017]
Liu, Y., Ye, X., Jiang, F., Liang, C., Chen, D., Peng, J., Kinch, L. N., Grishin, N. V., Liu, Q. C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation. Science 325: 750-753, 2009. [PubMed: 19661431] [Full Text: https://doi.org/10.1126/science.1176325]