# Intragenic suppressors of the C. elegans clk-2(qm37) mutation

## TL;DR

Researchers found mutations in the C. elegans CLK-2 gene that rescue harmful effects of a temperature-sensitive mutation, improving survival and fertility.

## Contribution

Identification of intragenic suppressor mutations in CLK-2 that restore function to a defective allele.

## Key findings

- Eight intragenic suppressor mutations were identified, with A828T being the most effective.
- Suppressor mutations stabilize the CLK-2(C772Y) protein and increase its accumulation.
- Rescue of viability and fertility at 25°C was observed with all suppressor mutations.

## Abstract

The

C. elegans

gene

clk-2

, which encodes the orthologue of yeast Tel2p and human TELO2, is implicated in development, lifespan, and telomere length regulation, among other functions. The thermosensitive allele

clk-2
(
qm37
)

(C772Y) is lethal and sterile at 25 °C. We identified eight intragenic mutations that rescue

qm37

defects in suppressor screens. Six yield an A828T substitution, one A828V, and one S859N. All restore viability and fertility at 25 °C, with A828T conferring the most efficient suppression at higher temperature. AlphaFold modeling of the proteins encoded by

clk-2
(
qm37
)

and suppressor mutations points to suppressors stabilizing the
CLK-2
(C772Y) protein, and suppression correlates with increased protein accumulation.