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

Yael Ziv, Anat Bar-Shira, Timothy J. Jorgensen, Pamela S. Russell, Adam Sartiel, Thomas B. Shows, Roger L. Eddy, Manuel Buchwald, Randy Legerski, Robert T. Schimke, Yosef Shiloh

Research output: Contribution to journalArticle

Abstract

Genes responsible for genetic diseases with increased sensitivity to DNA-damaging agents can be identified using complementation cloning. This strategy is based on in vitro complementation of the cellular sensitivity by gene transfer. Ataxia-telangiectasia (A-T) is a multisystem autosomal recessive disorder involving cellular sensitivity to ionizing radiation and radiomimetic drugs. A-T is genetically heterogeneous, with four complementation groups. We attempted to identify cDNA clones that modify the radiomimetic sensitivity of A-T cells assigned to complementation group [A-T(A)]. The cells were transfected with human cDNA libraries cloned in episomal vectors, and various protocols of radiomimetic selection were applied. Thirteen cDNAs rescued from survivor cells were found to confer various degrees of radiomimetic resistance to A-T(A) cells upon repeated introduction, and one of them also partially influenced another feature of the A-T phenotype, radioresistant DNA synthesis. None of the clones mapped to the A-T locus on chromosome 11q22-23. Nine of the clones were derived from known genes, some of which are involved in cellular stress responses. We concluded that a number of different genes, not necessarily associated with A-T, can influence the response of A-T cells to radiomimetic drugs, and hence the complementation cloning approach may be less applicable to A-T than to other diseases involving abnormal processing of DNA damage.

Original languageEnglish (US)
Pages (from-to)99-111
Number of pages13
JournalSomatic Cell and Molecular Genetics
Volume21
Issue number2
DOIs
StatePublished - Mar 1995

    Fingerprint

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Ziv, Y., Bar-Shira, A., Jorgensen, T. J., Russell, P. S., Sartiel, A., Shows, T. B., Eddy, R. L., Buchwald, M., Legerski, R., Schimke, R. T., & Shiloh, Y. (1995). Human cDNA clones that modify radiomimetic sensitivity of ataxia-telangiectasia (group A) cells. Somatic Cell and Molecular Genetics, 21(2), 99-111. https://doi.org/10.1007/BF02255785