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Human cDNA clones that modify radiomimetic sensitivity of ataxia-telangiectasia (group A) cells

Y Ziv1, A Bar-Shira, T J Jorgensen

  • 1Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Somatic Cell and Molecular Genetics
|March 1, 1995
PubMed

Insights

Complementation cloning identified thirteen cDNAs that altered radiomimetic drug sensitivity in Ataxia-telangiectasia (A-T) cells. This suggests multiple genes, not solely A-T related, influence cellular responses to DNA damage.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cell Biology

Background:

  • Ataxia-telangiectasia (A-T) is a genetic disorder characterized by sensitivity to DNA-damaging agents.
  • Genetic heterogeneity exists in A-T, with at least four complementation groups identified.
  • Complementation cloning is a strategy to identify genes responsible for cellular sensitivity to DNA damage.

Purpose of the Study:

  • To identify complementary DNA (cDNA) clones that modify the sensitivity of A-T cells (complementation group A) to radiomimetic drugs.
  • To investigate the applicability of complementation cloning for identifying genes involved in A-T.

Main Methods:

  • Transfection of A-T cells with human cDNA libraries cloned in episomal vectors.
  • Application of various radiomimetic drug selection protocols to isolate resistant cells.
  • Analysis of rescued cDNAs for their ability to confer resistance and influence A-T phenotypes.

Main Results:

  • Thirteen cDNAs were identified that conferred varying degrees of radiomimetic resistance to A-T(A) cells.
  • One cDNA clone also partially affected radioresistant DNA synthesis, another A-T phenotype.
  • None of the identified cDNAs mapped to the known A-T locus on chromosome 11q22-23.
  • Nine cDNAs were derived from known genes, some involved in cellular stress responses.

Conclusions:

  • Multiple genes, not necessarily directly linked to Ataxia-telangiectasia, can influence the response of A-T cells to radiomimetic drugs.
  • The complementation cloning approach may have limitations in identifying A-T-specific genes due to the involvement of numerous cellular pathways.
  • Further research is needed to fully understand the genetic basis of A-T and its complex cellular responses to DNA damage.

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