CHROMOSOMAL INSTABILITY AND ALTERATION OF TELOMERE REPEAT SEQUENCES

The very end of the chromosome is called the telomere and is composed of DNA repeat sequences and associated proteins. Genetic and biochemic al analyses of this complex, the telosome, lead to the hypothesis that transcription and DNA replication are submitted to position effects m ediated by the telomere proximity. Telomere length reduction and alter ations of the telomeric chromatin assembly might explain the chromosom e instability which occurs during the senescence and the immortalizati on process in vitro. A particular polymerase, the telomerase, is able to lengthen the telomeres. A telomerase activity was characterized in yeast, Tetrahymena, but also in transformed and in germline cells. We reviewed the involvement of telomeres in the aging process. We propose d that the short size of the telomere repeat at each chromosome could direct the loss of heterozygosity, thus telomere length could play a r ole in individual and tissular susceptibility to develop cancer. Antit elomerase strategy for cancer therapy is attractive but limited by the short decrease of the telomere length at each cell division.