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Damaged Telomere Elongation Analysis Points to Potential Cancer Treatment Target

In a paper appearing in PNAS this week, a University of Lisbon team describes diminished telomere integrity in the presence of cancer-related alternative lengthening of telomeres (ALT), which could be combated by targeting a related telomeric repeat-containing RNA. The damaged telomere elongation occurs via a break-induced replication, the researchers explain, noting that cell line experiments, fluorescence in situ hybridization analyses, qRT-PCR, gene expression profiling, and other approaches suggest ALT activity can be dialed down by reducing transcription of a telomeric, long non-coding RNA known as TERRA. Based on these and other results, the authors conclude that ALT "has to be kept under control to allow telomere elongation and indefinite cell proliferation without excessive telomere loss," and suggest that "TERRA transcription represents an exceptionally versatile target for ALT cancer therapy; indeed, both increasing and decreasing TERRA transcription should hinder cancer cell proliferation by compromising telomere maintenance."