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Identification of Alu transposition in human lung carcinoma cells

C S Lin1, D A Goldthwait, D Samols

  • 1Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.

Cell
|July 15, 1988
PubMed

Insights

Researchers demonstrated genetic transposition in human cells using a novel experimental system. UV irradiation significantly enhanced the inactivation of the Ecogpt (gpt) gene, revealing Alu sequence insertion.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Genetic transposition, the movement of DNA segments, is crucial for genome evolution.
  • Understanding transposition mechanisms in human cells is vital for genetic research.
  • The Ecogpt (gpt) gene serves as a reliable target for studying gene inactivation.

Purpose of the Study:

  • To demonstrate and analyze genetic transposition in human cells.
  • To investigate the effect of UV irradiation on gene inactivation frequency.
  • To characterize the nature of inserted genetic elements.

Main Methods:

  • Established a fusion system between human lung carcinoma A549 cells containing the Ecogpt (gpt) target and UV-irradiated A549 cells.
  • Analyzed sublines derived from fusion products for inactivated gpt genes.
  • Sequenced inserted elements to identify their origin and characteristics.

Main Results:

  • UV irradiation increased gpt gene inactivation frequency by 100-fold in fusion cells.
  • Identified a subline with a complete Alu sequence inserted into the gpt gene's coding region.
  • The inserted Alu element showed high similarity to the Blur8 sequence, differing by only 7 nucleotides.
  • Observed a 5 bp insertion site duplication associated with the Alu element insertion.

Conclusions:

  • Genetic transposition can be induced and studied in human cells.
  • UV irradiation is a potent enhancer of genetic transposition events.
  • Alu sequences are capable of transposing into functional genes, leading to inactivation and demonstrating potential mechanisms for genetic variation.

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