To the editor:

In a Letter in the July issue (Nat. Biotechnol. 22, 871–876, 2004), Martin Zeidler et al. describe a new approach for generating temperature-sensitive alleles based on conditionally active inteins. The system described is undoubtedly a novel and valuable alternative to 'classical' temperature-sensitive alleles. The authors of the Letter, as well as Francine Perler in an accompanying News and Views article (Nat. Biotechnol. 22, 824–826, 2004), discuss in detail the advantages of the intein-based system over classical temperature-sensitive alleles. However, both Zeidler et al. and Perler neglect to mention that one alternative to the classical temperature-sensitive allele has already been described and successfully used.

This approach is based on the use of a 'heat-inducible degron' cassette that is fused to the protein of interest and causes degradation of the degron together with the fused protein upon the temperature shift1. It has been successfully used in both budding2 and fission yeasts3,4, and it can also be used in large-scale analyses5.