HUMAN CDNA CLONES THAT MODIFY RADIOMIMETIC SENSITIVITY OF ATAXIA-TELANGIECTASIA (GROUP-A) CELLS

Citation
Y. Ziv et al., HUMAN CDNA CLONES THAT MODIFY RADIOMIMETIC SENSITIVITY OF ATAXIA-TELANGIECTASIA (GROUP-A) CELLS, Somatic cell and molecular genetics, 21(2), 1995, pp. 99-111
Citations number
57
Categorie Soggetti
Cell Biology","Genetics & Heredity",Biology
ISSN journal
07407750
Volume
21
Issue
2
Year of publication
1995
Pages
99 - 111
Database
ISI
SICI code
0740-7750(1995)21:2<99:HCCTMR>2.0.ZU;2-Z
Abstract
Genes responsible for genetic diseases with increased sensitivity to D NA-damaging agents can be identified using complementation cloning. Th is strategy is based on in vitro complementation of the cellular sensi tivity by gene transfer Ataxia-telangiectasia (A-T) is a multisystem a utosomal recessive disorder involving cellular sensitivity to ionizing radiation and radiomimetic drugs. A-T is genetically heterogeneous wi th four complementation groups. We attempted to identify, cDNA clones that modify the radiomimetic sensitivity of A-T cells assigned to comp lementation group [A-T(A)]. The cells were transfected with human cDNA libraries cloned in episomal vectors and various protocols of radiomi metic selection were applied. Thirteen cDNAs rescued from survivor cel ls were found to confer various degrees of radiomimetic resistance to A-T(A) cells upon repeated introduction, and one of them also partiall y influenced another feature of the A-T phenotype, radioresistant DNA synthesis. None of the clones mapped to the A-T locus on chromosome 11 q22-23. Nine of the clones were derived from known genes, some of whic h are involved in cellular stress responses. We concluded that a numbe r of different genes, not necessarily associated with A-T, can influen ce the response of A-T cells to radiomimetic drugs, and hence the comp lementation cloning approach may be less applicable to A-T than to oth er diseases involving abnormal processing of DNA damage.