Biopolym. Cell. 2008; 24(2):112-122.
Structure and Function of Biopolymers
Structural analysis of possible target-sites of RAG1/2 protein, discovered in mouse genome in silico, and their identification in repeating elements
1Gubsky A. Yu., 2Zinkovsky V. G.
  1. Odessa I. I. Mechnikov National University
    Dvoryanskaya Str., 2, Odessa, Ukraine, 65082
  2. Opole University
    pl. Kopernika 11a, Opole, Poland, 45-040

Abstract

We have established that the quantity of possible target-sites of RAG1/2 (cRSS) is 5.4 times higher than theoretically expected one using mathematical methods and specially developed algorithms. 71% of cases revealed cRSS in the structure of 390 types of repeats. The structure of 5% motives includes nucleotides, typical for the majority of signal sequences of recombination of functional V, D, J segments of Ig, Tcr mouse genes (fRSS). The existence of 25 % of such motives in mouse DNA may be considered as the consequence of random nucleotide combinations. In the majority of cases the structures of spacers 12cRSS and 23cRSS are 58–67 % and 30–47 % homologous to spacers 12fRSS and 23fRSS respectively.
Keywords: cRSS, V(D)J-recombination, RAG1, RAG2

References

[1] Tonegawa S. Somatic generation of antibody diversity. Nature. 1983;302(5909):575-81.
[2] Tonegawa S, Brack C, Hozumi N, Pirrotta V. Organization of immunoglobulin genes. Cold Spring Harb Symp Quant Biol. 1978;42 Pt 2:921-31.
[3] Oettinger MA, Schatz DG, Gorka C, Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990;248(4962):1517-23.
[4] Aplan PD, Lombardi DP, Ginsberg AM, Cossman J, Bertness VL, Kirsch IR. Disruption of the human SCL locus by "illegitimate" V-(D)-J recombinase activity. Science. 1990;250(4986):1426-9.
[5] Tsuji H, Ishii-Ohba H, Katsube T, Ukai H, Aizawa S, Doi M, Hioki K, Ogiu T. Involvement of illegitimate V(D)J recombination or microhomology-mediated nonhomologous end-joining in the formation of intragenic deletions of the Notch1 gene in mouse thymic lymphomas. Cancer Res. 2004;64(24):8882-90.
[6] Scheerer JB, Xi L, Knapp GW, Setzer RW, Bigbee WL, Fuscoe JC. Quantification of illegitimate V(D)J recombinase-mediated mutations in lymphocytes of newborns and adults. Mutat Res. 1999;431(2):291-303.
[7] Gubskiy AY. Structural analysis of recombination signal sequences of the three types of V-, D-, J-gene segments of immunoglobulin and T-cell receptors person. Odessa. Med. Zh. 2005; 5:10-12.
[8] Matsuda F, Ishii K, Bourvagnet P, Kuma Ki, Hayashida H, Miyata T, Honjo T. The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus. J Exp Med. 1998;188(11):2151-62.
[9] Lewis SM, Agard E, Suh S, Czyzyk L. Cryptic signals and the fidelity of V(D)J joining. Mol Cell Biol. 1997;17(6):3125-36.
[10] Cowell LG, Davila M, Yang K, Kepler TB, Kelsoe G. Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling. J Exp Med. 2003;197(2):207-20.
[11] Gubskiy AY, Zynkovskyy VG. Finding and identifying areas of localization in the mouse genome sequence cRSS, whose structure suggests a high recombination potential. Odessa Med zhurn. 2006;98(6):11-14.
[12] Hawley DK, McClure WR. Compilation and analysis of Escherichia coli promoter DNA sequences. Nucleic Acids Res. 1983;11(8):2237-55.
[13] Stormo GD. DNA binding sites: representation and discovery. Bioinformatics. 2000;16(1):16-23.
[14] Harr R, Haggstrom M, Gustafsson P. Search algorithm for pattern match analysis of nucleic acid sequences. Nucleic Acids Res. 1983;11(9):2943-57.
[15] Altschul SF, Madden TL, Sch?ffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25(17):3389-402.
[16] Jurka J. Repbase update: a database and an electronic journal of repetitive elements. Trends Genet. 2000;16(9):418-20.
[17] Fanning L, Connor A, Baetz K, Ramsden D, Wu GE. Mouse RSS spacer sequences affect the rate of V(D)J recombination. Immunogenetics. 1996;44(2):146-50.
[18] Akamatsu Y, Tsurushita N, Nagawa F, Matsuoka M, Okazaki K, Imai M, Sakano H. Essential residues in V(D)J recombination signals. J Immunol. 1994;153(10):4520-9.