Is the shortening of chromosome ends a trigger for radiation-induced senescence or genetic instability?

Telomeres are the physical ends of the linear eukaryotic chromosomes. Telomere erosion during DNA replication is considered to be the main cause of the onset of replicative senescence, an irreversible cell cycle arrest at the end of the lifespan of normal cells (1). With the help of a number of proteins, including the telomere repeat-binding factor 2 (TRF2), the telomeres form loop structures (Tloop) thereby avoiding being recognized as DNA strand breaks and preventing end-to-end telomere fusion (2). The latter is considered as a sign of genetic instability and demonstrates the crucial role of telomeres in preventing genetic instability. Telomere fusion can lead to dicentric chromosomes without fragments. Several months after exposure to Xrays, a large amount of cells with dicentric chromosomes were detected in the progeny of irradiated fibroblasts during our longterm experiments. In other cells, replicative senescence was observed (3). This is in line with published data, reporting that both replicative senescence and genetic instability can also be induced by others than cellintrinsic factors, among them external factors causing DNA damage (1). In our study presented here we were interested whether telomere shortening is detectable in the progeny of irradiated fibroblasts and, if so, whether the observed shortening is a basis for the occurrence of replicative senescence and genetic instability.