The Burden of Senescent Dysfunctional Telomeres in Normal Cells – a Pilot Study

Abstract

Introduction: Dysfunctional telomeres are critical for human health. They can be identified by their length, prevalence of telomeric variant repeats and frequency of damage localised to the telomeres, marked by the presence of ï§-H2AX.

Material and Methods: Using the metaphase Telomere dysfunctionInduced Foci (mTIF) assay, this study investigated the presence of TCAGGG, a telomeric variant repeat, and its association with the canonical repeat (TTAGGG) in a human cancer cell line (HT1080) and a normal cell strain (MRC-5) overtime (120 days).

Results: Due to cell growth arrest that accompanies cellular senescence, MRC-5 late population doublings (PD) show particularly short telomere length (TL) when compared to HT1080 in any stage and to MRC-5 early PD. Cancer cells displayed higher levels of TCAGGG, both alone and colocalised to the canonical repeat. HT1080 and MRC-5 late PD cells showed increased levels of ï§-H2AX colocalised to the canonical, to the variant repeat, and to both canonical and variant combined, when compared to MRC-5 early PD.

Conclusion: This pilot study identified that the fibrosarcoma cell line HT1080 is more susceptible to telomeric variant repeats occurrence, while normal late cells display higher levels dysfunctional telomeres, characterised by shorter TL and increased ï§-H2AX presence.