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Mol Med. 1997 November; 3(11): 740–749.
PMCID: PMC2230240

Molecular characterization of a mouse genomic element mobilized by advanced glycation endproduct modified-DNA (AGE-DNA).


BACKGROUND: DNA modified by advanced glycation endproducts (AGEs) undergoes a high frequency of insertional mutagenesis. In mouse lymphoid cells, these mutations are due in part to the transposition of host genomic elements that contain a DNA region homologous to the Alu family of repetitive elements. One particular 853 bp insertion, designated INS-1, was identified previously as a DNA element common to plasmids recovered from multiple, independent lymphoid cell transfections. MATERIALS AND METHODS: To characterize the genomic origin of this element, we used a 281-bp region of non-Alu-containing INS-1 sequence, designated. CORE, as a probe in Southern hybridization and for screening a bacteriophage mouse genomic DNA library. The resultant clones were sequenced and localized within the mouse genome. RESULTS: Two distinct genomic clones of 15 kB and 17 kB in size were isolated. A 522-bp unique region common to INS-1 and corresponding to the CORE sequence was identified in each clone. In both cases, CORE was found to be surrounded by repetitive DNA sequences: a 339-bp MT repeat at the 5' end, and a 150-bp B1 repeat at the 3' end. The CORE sequence was localized to mouse chromosome 1. CONCLUSIONS: These studies revealed that the CORE region of INS is present in low copy number but is associated with known repetitive DNA elements. The presence of these repetitive elements may facilitate the transposition of CORE by recombination or other, more complex rearrangement events, and explain in part the origin of AGE-induced insertional mutations.

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Selected References

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  • Bucala R, Lee AT, Rourke L, Cerami A. Transposition of an Alu-containing element induced by DNA-advanced glycosylation endproducts. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2666–2670. [PubMed]
  • Bucala R, Model P, Cerami A. Modification of DNA by reducing sugars: a possible mechanism for nucleic acid aging and age-related dysfunction in gene expression. Proc Natl Acad Sci U S A. 1984 Jan;81(1):105–109. [PubMed]
  • Bucala R, Model P, Russel M, Cerami A. Modification of DNA by glucose 6-phosphate induces DNA rearrangements in an Escherichia coli plasmid. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8439–8442. [PubMed]
  • Lee AT, Cerami A. Elevated glucose 6-phosphate levels are associated with plasmid mutations in vivo. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8311–8314. [PubMed]
  • Lee AT, Cerami A. Induction of gamma delta transposition in response to elevated glucose-6-phosphate levels. Mutat Res. 1991 Jul;249(1):125–133. [PubMed]
  • Bucala R, Cerami A. Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol. 1992;23:1–34. [PubMed]
  • Yanisch-Perron C, Vieira J, Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. [PubMed]
  • Pearson WR, Lipman DJ. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. [PubMed]
  • Bishop DT. The information content of phase-known matings for ordering genetic loci. Genet Epidemiol. 1985;2(4):349–361. [PubMed]
  • Adiletta DC, Elliott RW, Woodworth ME. Characterization of murine middle repetitive DNA. DNA Cell Biol. 1993 May;12(4):319–327. [PubMed]
  • Kiyama R, Matsui H, Oishi M. A repetitive DNA family (Sau3A family) in human chromosomes: extrachromosomal DNA and DNA polymorphism. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4665–4669. [PubMed]
  • Ohki R, Oishi M, Kiyama R. Preference of the recombination sites involved in the formation of extrachromosomal copies of the human alphoid Sau3A repeat family. Nucleic Acids Res. 1995 Dec 25;23(24):4971–4977. [PMC free article] [PubMed]
  • Calabretta B, Robberson DL, Barrera-Saldaña HA, Lambrou TP, Saunders GF. Genome instability in a region of human DNA enriched in Alu repeat sequences. Nature. 1982 Mar 18;296(5854):219–225. [PubMed]
  • 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 Oct 11;17(19):7631–7642. [PMC free article] [PubMed]
  • de Klein A, van Agthoven T, Groffen C, Heisterkamp N, Groffen J, Grosveld G. Molecular analysis of both translocation products of a Philadelphia-positive CML patient. Nucleic Acids Res. 1986 Sep 11;14(17):7071–7082. [PMC free article] [PubMed]
  • Shinder GA, Manam S, Ledwith BJ, Nichols WW. Minisatellite DNA-binding proteins in mouse brain, liver, and kidney. Exp Cell Res. 1994 Jul;213(1):107–112. [PubMed]
  • Watson ML, D'Eustachio P, Mock BA, Steinberg AD, Morse HC, 3rd, Oakey RJ, Howard TA, Rochelle JM, Seldin MF. A linkage map of mouse chromosome 1 using an interspecific cross segregating for the gld autoimmunity mutation. Mamm Genome. 1992;2(3):158–171. [PubMed]
  • DeBry RW, Seldin MF. Human/mouse homology relationships. Genomics. 1996 May 1;33(3):337–351. [PubMed]
  • Papoulis A, al-Abed Y, Bucala R. Identification of N2-(1-carboxyethyl)guanine (CEG) as a guanine advanced glycosylation end product. Biochemistry. 1995 Jan 17;34(2):648–655. [PubMed]
  • Sargent RG, Brenneman MA, Wilson JH. Repair of site-specific double-strand breaks in a mammalian chromosome by homologous and illegitimate recombination. Mol Cell Biol. 1997 Jan;17(1):267–277. [PMC free article] [PubMed]

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