PLOS Genetics study shows RPA–TERT–Tpz1 complex is required for productive telomerase engagement in fission yeast

A study published in PLOS Genetics presents genetic and structural modelling evidence for a tripartite complex involving Replication Protein A (RPA), the catalytic subunit of telomerase (TERT, encoded by Trt1 in fission yeast), and the telomere-capping protein Tpz1 — the fission yeast orthologue of human TPP1 — in the activation of telomere extension.

Telomerase maintains chromosome ends by adding repetitive DNA sequences to telomeres, counteracting the shortening that occurs with each cell division. A fundamental unresolved question has been how telomerase, once recruited to the telomere, transitions from a recruited to an actively elongating state. Recent work in human cells showed that RPA contributes to telomerase stimulation via interaction with TERT, and work in budding yeast implicated RPA in interactions with the TPP1 orthologue Est3.

The work by Moser, Points, and colleagues at the University of Illinois Chicago now provides evidence in fission yeast that RPA acts at the intersection of both these interactions — forming a complex with both TERT and Tpz1 to promote productive telomerase engagement. Loss of this complex results in impaired telomere extension and a switch towards recombination-based telomere maintenance.

The findings extend understanding of how telomerase activation is regulated across eukaryotes and may inform future research into telomere biology in human cells, including in the context of cancer-related telomere maintenance mechanisms.