Tk. Pandita et al., CHROMOSOME END ASSOCIATIONS, TELOMERES AND TELOMERASE ACTIVITY IN ATAXIA-TELANGIECTASIA CELLS, Cytogenetics and cell genetics, 71(1), 1995, pp. 86-93
Cells derived from individuals with ataxia telangiectasia (AT) show en
hanced spontaneous levels of chromosomal abnormalities and are sensiti
ve to ionizing radiations and radiomimetic drugs, as evidenced by decr
eased survival and increased chromosome aberration frequencies at mito
sis when compared with normal cell lines. The higher base line frequen
cies of chromosome aberrations in part involve chromosome end-to-end a
ssociations as seen at metaphase. Since telomeres of tumor cells and a
ging tissues are often reduced in length, chromosome end associations
may be due to loss of telomeric repeats. We studied the chromosome beh
avior and telomeres of two ataxia telangiectasia lymphoblastoid cell l
ines compared to two normal control cell lines. The ataxia telangiecta
sia cell lines showed higher frequencies of chromosome end association
s both at metaphase and in interphase, determined in prematurely conde
nsed chromosomes of G(1) and G(2) cells. They also showed higher frequ
encies of chromosomal breaks at metaphase and fewer telomeric signals
determined using fluorescent in situ hybridization with a (TTAGGG)(n)
probe. The frequency of telomeric repeats was variable in the ataxia t
elangiectasia cell lines (4.3 and 8.2 kb) compared to the normal cell
lines (9.6 and 12 kb) and an inverse correlation between telomere leng
th and chromosome end associations was observed. Both ataxia telangiec
tasia cell lines showed more robust telomerase activity than the norma
l cell lines, precluding defective enzymatic capacity as the basis for
the chromosome end associations. It is possible that chromatin struct
ure in the form of telomere-nuclear matrix interactions are variant in
ataxia telangiectasia cells negatively influencing telomerase functio
n and contributing to telomere associations.