How does a protein complex ensure accurate DNA replication? This study investigates the role of the Xrs2 complex in *Saccharomyces cerevisiae* (yeast), a counterpart to the human Nbs1 complex involved in DNA repair. The research demonstrates that *xrs2*Δ, *mre11*Δ, and *rad50*Δ mutants are defective in initiating the intra-S phase checkpoint in response to DNA damage. The study reveals that the absence of a functional Xrs2p complex results in sensitivity to deoxynucleotide depletion and impairs cell cycle progression in response to hydroxyurea. The checkpoint requires the nuclease activity of Mre11p and associates with the abrogation of the Tel1p/Mec1p signaling pathway. DNA damage induces phosphorylation of both Xrs2p and Mre11p in a Tel1p-dependent manner. This suggests a conserved signaling pathway. These results suggest that the Tel1p/ATM signaling pathway is conserved from yeast to humans and indicate that the Xrs2p/Nbs1 complexes act as signal modifiers. These results provide new insight for human and environmental biology.
Published in Genes & Development, this research aligns with the journal's focus on molecular biology, genetics, and cell cycle regulation. The study's exploration of the Xrs2 complex and its role in DNA damage response is highly relevant to the journal's scope and audience.