Yaf9 connects NuA4 and SWR1 functions to maintain genome integrity

Precise regulation of chromatin structure is essential for ensuring genome stability and cellular function. In Saccharomyces cerevisiae, the YEATS (Yaf9-ENL-AF9-Taf14-Sas5) domain protein Yaf9 is a shared component of the NuA4 acetyltransferase and the SWR1 chromatin remodeling complexes. We investigated the function of Yaf9 and discovered that it becomes essential for survival when histone H4 acetylation is impaired. The loss of Yaf9 in a strain with impaired H4 acetylation led to cell cycle arrest in the G2/M phase and activation of the homologous recombination pathway. This synthetic lethality was not recapitulated by inactivating the Yaf9 YEATS domain, suggesting that it is independent of Yaf9's ability to recognize acyl-modified lysine residues. We also found that Yaf9 was required in both NuA4 and SWR1 complexes to ensure cell viability in the absence of H4 acetylation. Together, these findings reveal a compensatory relationship between Yaf9 and histone H4 acetylation, suggesting that Yaf9 acts as a functional link between chromatin remodeling and histone modification pathways to maintain genome integrity under conditions of chromatin stress.