Telomere Instability Induced by Anticancer Drugs in Mammalian Cells

Telomere instability results from chromosome end loss (due to chromosome breakage at one or both ends) or, more frequently, telomere dysfunction. Dysfunctional telomeres arise when they lose their end-capping function or become critically short, which causes chromosomal termini to behave like a DNA double-strand break. At the chromosomal level, this phenomenon is visualized by using Fluorescence In Situ Hybridization (FISH), as chromosomal aberrations directly involving terminal telomeric repeats: loss or dupli‐ cation of telomeric signals, association or fusion of telomeres of different chromosomes, telomere sister chromatid exchanges, translocation or amplification of telomeric sequen‐ ces, and extrachromosomal telomeric signals. At the molecular level, telomere instability arises due to the loss or modification of any of the components of the telomere (telomere DNA, telomere-associated proteins or telomere RNA). Since telomeres play a fundamen‐ tal role in maintaining genomic stability, the study of telomere instability in cells exposed to anticancer drugs is of great importance to understand the genomic instability associat‐ ed with chemotherapy regimens. In this chapter, we will summarize our current knowl‐ edge about telomere instability induced by anticancer drugs on mammalian cells.