Dun1

Dun1 (DNA damage and replication checkpoint 1) is a serine/threonine protein kinase in the budding yeast Saccharomyces cerevisiae. It is a key component of the DNA damage and replication stress response, functioning in the Mec1–Rad53–Dun1 signaling axis and acting downstream of Mec1 and Rad53. The primary established role of Dun1 is to promote dNTP accumulation during DNA damage by phosphorylating Sml1, an inhibitor of ribonucleotide reductase, which targets Sml1 for ubiquitin-mediated degradation and relieves inhibition of ribonucleotide reductase. This increase in dNTP pools supports DNA replication and repair under stress.

Dun1 also contributes to the transcriptional response to damage by promoting the induction of ribonucleotide reductase genes, in part by modulating Crt1, a transcriptional repressor of RNR genes, enabling greater dNTP synthesis. Genetic analyses show that dun1-null mutants exhibit sensitivity to DNA damaging agents and replication stress, and place DUN1 within the checkpoint pathway alongside Mec1 and Rad53. The DUN1 gene was identified in yeast genetic screens in the 1990s, and its protein is part of a conserved network that maintains genome integrity in the face of damage and replication perturbations.