PLoS geneticsSep 8, 2026

A protein complex in fission yeast helps lengthen chromosome ends and prevent their rearrangement

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 9, 2026

Abstract

A ternary complex involving RPA, Trt1, and Tpz1 promotes telomere extension and suppresses recombination in fission yeast.

Genetic and structural modeling evidence indicates that RPA interacts with Trt1 and Tpz1 to enhance telomerase function.
Four key interfaces supporting telomerase activity were identified: Ssb1RPA1-Trt1, Ssb2RPA2-Trt1, Ssb2RPA2-Tpz1, and the TEL-patch-mediated Trt1-Tpz1 interaction.
The interaction of Tpz1-R81, previously thought to be part of the TEL patch, is instead shown to contact Ssb2.
Epistasis and suppressor analyses suggest that RPA-Trt1 and RPA-Tpz1 interfaces work together with Trt1-Tpz1 to activate telomerase after it is recruited.
Comparative analyses imply that these interactions may also be conserved in budding yeast and humans.

Simplified

Telomerase maintains chromosome ends by extending telomeric DNA, yet how recruited telomerase becomes productively engaged remains poorly understood. Recent studies found that Replication Protein A (RPA) contributes to telomerase stimulation through interaction with TERT in humans and with the TPP1 ortholog Est3 in budding yeast, suggesting a direct role in telomerase activation. Here, we provide genetic and structural modeling evidence for a RPA-Trt1TERT-Tpz1TPP1 ternary complex that promotes telomere extension while suppressing recombination in fission yeast. Guided by results from genetic screen, followed by AlphaFold3 modeling and systematic mutagenesis of RPA, Trt1, and Tpz1, we identify four key interfaces supporting telomerase function: Ssb1RPA1-Trt1, Ssb2RPA2-Trt1, Ssb2RPA2-Tpz1, and the TEL-patch-mediated Trt1-Tpz1 interaction. Notably, Tpz1-R81, previously assigned as the TEL patch, instead contacts Ssb2 in the complex. Epistasis and suppressor analyses indicate that the newly identified RPA-Trt1 and RPA-Tpz1 interfaces collaborate with the Trt1-Tpz1 interface to allow telomerase activation after recruitment. Furthermore, comparative analyses using AlphaFold3 suggest that these interactions are likely conserved in budding yeast and humans. Collectively, these findings support a model in which RPA serves as an essential component of the active telomerase complex, coordinating TERT and TPP1-like factors to enable productive telomerase engagement.

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A protein complex in fission yeast helps lengthen chromosome ends and prevent their rearrangement

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