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
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.