The proliferative capacity of cells is defined by their telomere length, which typically shortens with each cell division. However, in germline, stem and ~85% of cancer cells, telomeres are elongated by the ribonucleoprotein telomerase, which allows these cells to replicate indefinitely. While the function of telomerase is reasonably well characterised, less is known about the processes which regulate its function, including its recruitment to telomeres. It has been demonstrated that the DNA damage response is important in regulating telomerase recruitment to telomeres, specifically via the regulatory kinases ATR and ATM, which coordinate the cellular response to DNA damage1,2. ATR is important for the cellular response to single-stranded DNA, which is typically produced as a by-product of replication stress (i.e. replication fork stalling). In addition to this, we have previously shown that replication stress promotes telomerase recruitment to the telomere in an ATR-dependent manner1. We have also recently identified that nuclear actin polymerisation is important for DNA replication dynamics, particularly following replication stress, in an ATR-dependent manner. Given this, we hypothesise that there is controlled interplay between DNA replication, the DNA damage response and telomere maintenance.
In this study we have demonstrated that downstream components of the ATR-mediated DNA damage response are important for recruitment of telomerase to telomeres. Furthermore, the polymerisation of actin is also necessary for this recruitment to occur efficiently. These results together suggest that telomerase is recruited to telomeres by actin via the DNA damage response. This supports a model of telomerase recruitment in which DNA replication and the DNA damage response are crucial factors which dictate the timing and occurrence of telomere maintenance.