Investigating the Regulation and Replication of R-loops at Telomeres

Eukaryotic chromosomes are capped at each end by specialised nucleoprotein structures called telomeres, which are mutated or altered in essentially all incidences of cancer. Telomeres are transcribed into a non-coding RNA called TERRA, which forms a three-stranded R-loop structure in which the RNA remains bound to the template. R-loops are particularly prevalent at telomeres in ALT-type cancer cells, where they are thought to prevent efficient replication of the chromosome end. This project will identify novel R-loop regulating factors at telomeres and examine how TERRA-based R-loops regulate and influence the telomere replication process.