FIGURE 4.

Activation of DNA damage checkpoint and cell cycle arrest in yeast. The activation of DNA damage checkpoint in S. cerevisiae requires detection of DSB by MRX complex and its processing by Sae2, Exo1, Sgs1, and Dna2 to generate 3′ ssDNA extension. Subsequently, the recruitment and activation of Mec1/Tel1 leads to the activation of Chk1, RAD53 and Dun1, resulting in the phosphorylation of securin Pds1 and protection from proteolytic degradation by E3 ubiquitin ligases APC^Cdc20 and Rsp5. The stabilized Pds1 inhibits the separase Esp1 and prevents sister chromatid separation, leading to cell cycle arrest. In parallel, the checkpoint activation also triggers the DNA repair pathways.