27. Telomeres and telomerase in radio-sensitivity and gene amplification

Abstract: Telomeres and telomerase play key roles in the maintenance of genome stability. Chiara Mondello, in collaboration with Elena Giulotto, has shown that in telomerase expressing cells, very short telomeres do not increase cellular and chromosomal radiosensitivity, as they do in telomerase negative cells. On the other hand, they have shown that in telomerase deficient mouse cells, gene amplification, a typical manifestation of genome instability observed in tumour cells, is not detectable, indicating that telomerase is required for the occurrence of this process. The lack of gene amplification in telomerase deficient cells could be due to the inability of the deficient cells to stabilize amplified chromosomes with new telomeres. Alternatively, telomerase could have an indirect role by controlling the expression of other genes involved in the process. These results highlight the complexity of the role of telomeres and telomerase in the preservation of genome integrity.

Since telomerase is expressed in the vast majority of the tumours, the indication that telomerase is essential for gene amplification suggests that the use of drugs inhibiting telomerase could also decrease the occurrence of gene amplification, thus reducing tumour aggressiveness. These aspects are particularly relevant for the future development of personalized therapeutic protocols.

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