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

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.