Biopolym. Cell. 1996; 12(2):7-19.
http://dx.doi.org/10.7124/bc.00041A
Reviews
Mobile genetic elements in mutagenic process, recombination and malignization of human cells
1Lukash L. L., 1Shvachko L. P., 1Kostetskaya K. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnogo Str., Kyiv, Ukraine, 252143

Abstract

Mutagenesis is known as the major stage of the complicated process of malignization. There are a lot of data in support of this idea, for example, all known cancerogenes are mutagenes. During several years microsatellite DNA instability was recognized as important trait of tumours. In this paper we reviewed the contribution of mobile genetic elements (human Alu repetitive sequences) in appearance of heritable and somatic diseases, including malignization. Localizingin «hotspot» of mutagenic andreconibinationevents Alu sequences appear to be genetic markers for the estimation of human genome instability.
Full text: (PDF, in Russian)

References

[1] Shapiro NI. Mutagenesis and carcinogenesis. Usp Sovrem Biol. 1967;63(2):163-83.
[2] Barrett JC, Ts'o PO. Relationship between somatic mutation and neoplastic transformation. Proc Natl Acad Sci U S A. 1978;75(7):3297-301.
[3] Lukash LL. Correlation of mutagenesis and malignant transformation. Evolutionary aspects. Genetic effects of environmental pollution. Kiev: Naukova Dumka, 1989: 121-143 (144-164).
[4] Spandidos DA, Anderson ML. Oncogenes and onco-suppressor genes: their involvement in cancer. J Pathol. 1989;157(1):1-10.
[5] McCormick F. Ras oncogenes in oncogenesis and molecular origin of cancer. Ed. R. A. Weinberg. New York: Cold Spring Harbor Lab., 1989: 125-145.
[6] Cole MD. The myc oncogene: its role in transformation and differentiation. Annu Rev Genet. 1986;20:361-84.
[7] Ramsay GM, Moscovici G, Moscovici C, Bishop JM. Neoplastic transformation and tumorigenesis by the human protooncogene MYC. Proc Natl Acad Sci U S A. 1990;87(6):2102-6.
[8] Bishop JM. Molecular themes in oncogenesis. Cell. 1991;64(2):235-48.
[9] Hunter T. Cooperation between oncogenes. Cell. 1991;64(2):249-70.
[10] Haluska FG, Tsujimoto Y, Croce CM. Oncogene activation by chromosome translocation in human malignancy. Annu Rev Genet. 1987;21:321-45.
[11] Cory S. Activation of cellular oncogenes in hemopoietic cells by chromosome translocation. Adv Cancer Res. 1986;47:189-234.
[12] Cleary ML. Oncogenic conversion of transcription factors by chromosomal translocations. Cell. 1991;66(4):619-22.
[13] Uryvaeva IV. Cell proliferation in the key events of carcinogenesis. Cell reproduction and differentiation processes. L.: Nauka, 1990: 94-109.
[14] Oncogenes and the molecular origins of cancer. Ed. R. A. Weinberg. New York: Cold Spring Harbor Lab., 1989. 367 p.
[15] Khesin RB. Genome instability. Moscow, Nauka, 1984; 472 p.
[16] Ayzenzon M. G., Aleksandrov YU. N., Buzhiyevskaya T. I, et al. Mutagenic effects of natural and synthetic polynucleotides. Kiev: Naukova dumka, 1990. 124 p.
[17] Rubashevski? EL, Patskovski? IuV, Podol'skaia SV, Sukhorada EM, Lysenko EF, Kostetskaia EV, Kostetski? IE, Varzanova IS, Lukash LL. The induction of mutations in 6-mercaptopurine resistance in Chinese hamster cells under the action of the recombinant plasmid pAins containing the human insulin gene. Tsitol Genet. 1993;27(3):63-8.
[18] Lukash LL, Podolskaya SV, Suhorada HM, Kostetskaya KV, Kostetsky IE, Varzanova IS, Patskovsky YuV, Vavilina IV, Deis SV. The influence of alkylating agent MNNG on mutagenic effect of exogeneous recombinant DNA. Biopolym Cell. 1995; 11(1):87-91.
[19] Karpova IS, Pidpala OV, Shul'zhenko VN, Kostetski? IE, Koretskaia NV, Lukash LL. The mutagenic activity of the DNA of recombinant plasmids in a competent Bacillus subtilis culture. Tsitol Genet. 1994;28(1):66-73.
[20] Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260(5109):816-9.
[21] Mao L, Lee DJ, Tockman MS, Erozan YS, Askin F, Sidransky D. Microsatellite alterations as clonal markers for the detection of human cancer. Proc Natl Acad Sci U S A. 1994;91(21):9871-5.
[22] Weber JL. Informativeness of human (dC-dA)n.(dG-dT)n polymorphisms. Genomics. 1990;7(4):524-30.
[23] Di Rienzo A, Peterson AC, Garza JC, Valdes AM, Slatkin M, Freimer NB. Mutational processes of simple-sequence repeat loci in human populations. Proc Natl Acad Sci U S A. 1994;91(8):3166-70.
[24] Bowcock A, Osborne-Lawrence S, Barnes R, Chakravarti A, Washington S, Dunn C. Microsatellite polymorphism linkage map of human chromosome 13q. Genomics. 1993;15(2):376-86.
[25] Zabarovsky ER, Kashuba VI, Pokrovskaya ES, Zabarovska VI, Wang JY, Berglund P, Boldog F, Stanbridge EJ, Sumegi J, Klein G, et al. Alu-PCR approach to isolating NotI-linking clones from the 3p14-p21 region frequently deleted in renal cell carcinoma. Genomics. 1993;16(3):713-9.
[26] Richards RI, Sutherland GR. Dynamic mutations: a new class of mutations causing human disease. Cell. 1992;70(5):709-12.
[27] La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991;352(6330):77-9.
[28] Kremer EJ, Pritchard M, Lynch M, Yu S, Holman K, Baker E, Warren ST, Schlessinger D, Sutherland GR, Richards RI. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science. 1991;252(5013):1711-4.
[29] Harley HG, Brook JD, Rundle SA, Crow S, Reardon W, Buckler AJ, Harper PS, Housman DE, Shaw DJ. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature. 1992;355(6360):545-6.
[30] Stine OC, Pleasant N, Franz ML, Abbott MH, Folstein SE, Ross CA. Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum Mol Genet. 1993;2(10):1547-9.
[31] Di Rienzo A, Peterson AC, Garza JC, Valdes AM, Slatkin M, Freimer NB. Mutational processes of simple-sequence repeat loci in human populations. Proc Natl Acad Sci U S A. 1994;91(8):3166-70.
[32] Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363(6429):558-61.
[33] Wallace SS, van Houten B, Wah Row Y. DNA damage. Effects on DNA structure and protein recognition. Ann N Y Acad Sci. 1994; 726. 385 p.
[34] Sweezy MA, Fishel R. Multiple pathways leading to genomic instability and tumorigenesis. Ann N Y Acad Sci. 1994;726:165-77.
[35] Modrich P. Mechanisms and biological effects of mismatch repair. Annu Rev Genet. 1991;25:229-53.
[36] Prolla TA, Pang Q, Alani E, Kolodner RD, Liskay RM. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994;265(5175):1091-3.
[37] Fang WH, Modrich P. Human strand-specific mismatch repair occurs by a bidirectional mechanism similar to that of the bacterial reaction. J Biol Chem. 1993;268(16):11838-44.
[38] Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993;75(6):1227-36.
[39] Orth K, Hung J, Gazdar A, Bowcock A, Mathis JM, Sambrook J. Genetic instability in human ovarian cancer cell lines. Proc Natl Acad Sci U S A. 1994;91(20):9495-9.
[40] Stanbridge EJ. Human tumor suppressor genes. Annu Rev Genet. 1990;24:615-57.
[41] Houck CM, Rinehart FP, Schmid CW. A ubiquitous family of repeated DNA sequences in the human genome. J Mol Biol. 1979;132(3):289-306.
[42] Schmid CW, Jelinek WR. The Alu family of dispersed repetitive sequences. Science. 1982;216(4550):1065-70.
[43] Zuckerkandl E, Latter G, Jurka J. Maintenance of function without selection: Alu sequences as "cheap genes". J Mol Evol. 1989;29(6):504-12.
[44] Kariya Y, Kato K, Hayashizaki Y, Himeno S, Tarui S, Matsubara K. Revision of consensus sequence of human Alu repeats--a review. Gene. 1987;53(1):1-10.
[45] Batzer MA, Kilroy GE, Richard PE, Shaikh TH, Desselle TD, Hoppens CL, Deininger PL. Structure and variability of recently inserted Alu family members. Nucleic Acids Res. 1990;18(23):6793-8.
[46] Labuda D, Striker G. Sequence conservation in Alu evolution. Nucleic Acids Res. 1989;17(7):2477-91.
[47] Paulson KE, Schmid CW. Transcriptional inactivity of Alu repeats in HeLa cells. Nucleic Acids Res. 1986;14(15):6145-58.
[48] Jurka J, Smith T. A fundamental division in the Alu family of repeated sequences. Proc Natl Acad Sci U S A. 1988;85(13):4775-8.
[49] Fuhrman SA, Deininger PL, LaPorte P, Friedmann T, Geiduschek EP. Analysis of transcription of the human Alu family ubiquitous repeating element by eukaryotic RNA polymerase III. Nucleic Acids Res. 1981;9(23):6439-56.
[50] Dalla-Favera R, Gelmann EP, Gallo RC, Wong-Staal F. A human onc gene homologous to the transforming gene (v-sis) of simian sarcoma virus. Nature. 1981;292(5818):31-5.
[51] Bell GI, Pictet R, Rutter WJ. Analysis of the regions flanking the human insulin gene and sequence of an Alu family member. Nucleic Acids Res. 1980;8(18):4091-109.
[52] Edwards A, Voss H, Rice P, Civitello A, Stegemann J, Schwager C, Zimmermann J, Erfle H, Caskey CT, Ansorge W. Automated DNA sequencing of the human HPRT locus. Genomics. 1990;6(4):593-608.
[53] Korenberg JR, Rykowski MC. Human genome organization: Alu, lines, and the molecular structure of metaphase chromosome bands. Cell. 1988;53(3):391-400.
[54] Comings DE. Mechanisms of chromosome banding and implications for chromosome structure. Annu Rev Genet. 1978;12:25-46.
[55] Morgan WF, Crossen PE. The frequency and distribution of sister chromatid exchanges in human chromosomes. Hum Genet. 1977;38(3):271-8.
[56] Kuhn EM, Therman E. Cytogenetics of Bloom's syndrome. Cancer Genet Cytogenet. 1986;22(1):1-18.
[57] Goldman MA, Holmquist GP, Gray MC, Caston LA, Nag A. Replication timing of genes and middle repetitive sequences. Science. 1984;224(4650):686-92.
[58] Johnson EM, Jelinek WR. Replication of a plasmid bearing a human Alu-family repeat in monkey COS-7 cells. Proc Natl Acad Sci U S A. 1986;83(13):4660-4.
[59] Nicholls RD, Fischel-Ghodsian N, Higgs DR. Recombination at the human alpha-globin gene cluster: sequence features and topological constraints. Cell. 1987;49(3):369-78.
[60] Mitchell GA, Labuda D, Fontaine G, Saudubray JM, Bonnefont JP, Lyonnet S, Brody LC, Steel G, Obie C, Valle D. Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation. Proc Natl Acad Sci U S A. 1991;88(3):815-9.
[61] Lehrman MA, Schneider WJ, S?dhof TC, Brown MS, Goldstein JL, Russell DW. Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science. 1985;227(4683):140-6.
[62] Lehrman MA, Russell DW, Goldstein JL, Brown MS. Alu-Alu recombination deletes splice acceptor sites and produces secreted low density lipoprotein receptor in a subject with familial hypercholesterolemia. J Biol Chem. 1987;262(7):3354-61.
[63] Shimada F, Taira M, Suzuki Y, Hashimoto N, Nozaki O, Taira M, Tatibana M, Ebina Y, Tawata M, Onaya T, et al. Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene. Lancet. 1990;335(8699):1179-81.
[64] Myerowitz R, Hogikyan ND. A deletion involving Alu sequences in the beta-hexosaminidase alpha-chain gene of French Canadians with Tay-Sachs disease. J Biol Chem. 1987;262(32):15396-9.
[65] Buckle VJ, Boyd Y, Fraser N, Goodfellow PN, Goodfellow PJ, Wolfe J, Craig IW. Localisation of Y chromosome sequences in normal and 'XX' males. J Med Genet. 1987;24(4):197-203.
[66] Morris T, Thacker J. Formation of large deletions by illegitimate recombination in the HPRT gene of primary human fibroblasts. Proc Natl Acad Sci U S A. 1993;90(4):1392-6.
[67] Monnat RJ Jr, Hackmann AF, Chiaverotti TA. Nucleotide sequence analysis of human hypoxanthine phosphoribosyltransferase (HPRT) gene deletions. Genomics. 1992;13(3):777-87.
[68] Markert ML, Hutton JJ, Wiginton DA, States JC, Kaufman RE. Adenosine deaminase (ADA) deficiency due to deletion of the ADA gene promoter and first exon by homologous recombination between two Alu elements. J Clin Invest. 1988;81(5):1323-7.
[69] L?zaro C, Gaona A, Ravella A, Volpini V, Casals T, Fuentes JJ, Estivill X. Novel alleles, hemizygosity and deletions at an Alu-repeat within the neurofibromatosis type 1 (NF1) gene. Hum Mol Genet. 1993;2(6):725-30.
[70] Elder JT, Pan J, Duncan CH, Weissman SM. Transcriptional analysis of interspersed repetitive polymerase III transcription units in human DNA. Nucleic Acids Res. 1981;9(5):1171-89.
[71] Rouyer F, Simmler MC, Page DC, Weissenbach J. A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination. Cell. 1987;51(3):417-25.
[72] Chen SJ, Chen Z, Font MP, d'Auriol L, Larsen CJ, Berger R. Structural alterations of the BCR and ABL genes in Ph1 positive acute leukemias with rearrangements in the BCR gene first intron: further evidence implicating Alu sequences in the chromosome translocation. Nucleic Acids Res. 1989;17(19):7631-42.
[73] Chen SJ, Chen Z, Hillion J, Grausz D, Loiseau P, Flandrin G, Berger R. Ph1-positive, bcr-negative acute leukemias: clustering of breakpoints on chromosome 22 in the 3' end of the BCR gene first intron. Blood. 1989;73(5):1312-5.
[74] Vergnaud G, Page DC, Simmler MC, Brown L, Rouyer F, Noel B, Botstein D, de la Chapelle A, Weissenbach J. A deletion map of the human Y chromosome based on DNA hybridization. Am J Hum Genet. 1986;38(2):109-24.
[75] Disteche CM, Casanova M, Saal H, Friedman C, Sybert V, Graham J, Thuline H, Page DC, Fellous M. Small deletions of the short arm of the Y chromosome in 46,XY females. Proc Natl Acad Sci U S A. 1986;83(20):7841-4.
[76] Vnencak-Jones CL, Phillips JA 3rd. Hot spots for growth hormone gene deletions in homologous regions outside of Alu repeats. Science. 1990;250(4988):1745-8.
[77] Muratani K, Hada T, Yamamoto Y, Kaneko T, Shigeto Y, Ohue T, Furuyama J, Higashino K. Inactivation of the cholinesterase gene by Alu insertion: possible mechanism for human gene transposition. Proc Natl Acad Sci U S A. 1991;88(24):11315-9.
[78] Goldberg YP, Rommens JM, Andrew SE, Hutchinson GB, Lin B, Theilmann J, Graham R, Glaves ML, Starr E, McDonald H, et al. Identification of an Alu retrotransposition event in close proximity to a strong candidate gene for Huntington's disease. Nature. 1993;362(6418):370-3.
[79] Ma TS, Ifegwu J, Watts L, Siciliano MJ, Roberts R, Perryman MB. Serial Alu sequence transposition interrupting a human B creatine kinase pseudogene. Genomics. 1991;10(2):390-9.
[80] Wallace MR, Andersen LB, Saulino AM, Gregory PE, Glover TW, Collins FS. A de novo Alu insertion results in neurofibromatosis type 1. Nature. 1991;353(6347):864-6.
[81] Nguyen T, Marchese A, Kennedy JL, Petronis A, Peroutka SJ, Wu PH, O'Dowd BF. An Alu sequence interrupts a human 5-hydroxytryptamine1D receptor pseudogene. Gene. 1993;124(2):295-301.
[82] Yang TP, Stout JT, Konecki DS, Patel PI, Alford RL, Caskey CT. Spontaneous reversion of novel Lesch-Nyhan mutation by HPRT gene rearrangement. Somat Cell Mol Genet. 1988;14(3):293-303.
[83] Murru S, Casula L, Pecorara M, Mori P, Cao A, Pirastu M. Illegitimate recombination produced a duplication within the FVIII gene in a patient with mild hemophilia A. Genomics. 1990;7(1):115-8.
[84] Lehrman MA, Goldstein JL, Russell DW, Brown MS. Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987;48(5):827-35.
[85] Hu XY, Burghes AH, Ray PN, Thompson MW, Murphy EG, Worton RG. Partial gene duplication in Duchenne and Becker muscular dystrophies. J Med Genet. 1988;25(6):369-76.
[86] Hu XY, Ray PN, Worton RG. Mechanisms of tandem duplication in the Duchenne muscular dystrophy gene include both homologous and nonhomologous intrachromosomal recombination. EMBO J. 1991;10(9):2471-7.
[87] Marcus S, Hellgren D, Lambert B, F?llstr?m SP, Wahlstr?m J. Duplication in the hypoxanthine phosphoribosyl-transferase gene caused by Alu-Alu recombination in a patient with Lesch Nyhan syndrome. Hum Genet. 1993;90(5):477-82.
[88] Monnat RJ Jr, Chiaverotti TA, Hackmann AF, Maresh GA. Molecular structure and genetic stability of human hypoxanthine phosphoribosyltransferase (HPRT) gene duplications. Genomics. 1992;13(3):788-96.
[89] Qin ZH, Schuller I, Richter G, Diamantstein T, Blankenstein T. The interleukin-6 gene locus seems to be a preferred target site for retrotransposon integration. Immunogenetics. 1991;33(4):260-6.
[90] Taruscio D, Manuelidis L. Integration site preferences of endogenous retroviruses. Chromosoma. 1991;101(3):141-56.
[91] Singh MK, Pauza CD. Extrachromosomal human immunodeficiency virus type 1 sequences are methylated in latently infected U937 cells. Virology. 1992;188(2):451-8.
[92] Matsumoto H, Yoneyama T, Mitamura K, Osuga T, Shimojo H, Miyamura T. Analysis of integrated hepatitis B virus DNA and cellular flanking sequences cloned from a hepatocellular carcinoma. Int J Cancer. 1988;42(1):1-6.
[93] Gershenson SM. “Egoistic” DNA, molecular drive and evolutionary problems. Tsitol Genet. 1993; 27(3):85-94.
[94] Golubovsky M. Mobile genetics and forms of heritable changes in eukaryotes. Biopolym Cell. 1995; 11(2):29-38.