Swc4 protects chromatin against genome instability and aneuploidy

In the baker’s yeast Saccharomyces cerevisiae, Swc4, Yaf9, Arp4, and Act1 form a submodule shared by histone acetylation NuA4 complex and chromatin remodeling SWR1 complex (SWR1-C). Act1 and Arp4 are essential for cell survival. Deletion of SWC4, but not YAF9, results in severe growth defect, however, the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display mitotic defects in both faithful chromosome segregation and DNA ploidy, suggesting that the defects observed in swc4Δ cells are independent of the integrity of either NuA4 or SWR1-C. Additionally, loss of Swc4 function results in chromosomal breakage, spindle assembly check-point activation and significant increase of the Rfa1 foci and γ-H2A levels. Notably, both telomeres and rDNA loci in swc4Δ cells become unstable and are highly susceptible to recombination. Mechanistically, Swc4 interacts with chromatin likely through hypoacetylated histone H4. Taking together, we conclude that the chromatin associated Swc4 protects chromatin from breakage to ensure genome integrity. Examination of the enrichment of myc tagged Swc4 on chromatin in the budding yeast.