In yeast, the ATP-dependent chromatin remodelers INO80 and SWR1 are major guardians of the genome (24) and prevent the accumulation of mutations, much as p53 does in mammalian cells. They have a critical role in double-strand break repair and also function in checkpoint pathways and nucleotide excision repair. Curiously, these complexes are similar to mammalian BAF complexes in that they contain β-actin and similar actin-related proteins (ARPs), which are most homologous to BAF53a and BAF53b. Thus, they may be structurally and functionally related to vertebrate BAF complexes. Although their importance in genome maintenance is clear, their mammalian homologs are not commonly mutated in human cancer. This may reflect the fact that BAF subunits are genetically dominant and dosage-sensitive and, hence, represent a significant organismic susceptibility. Genes that are frequently mutated in a disease are not necessarily more important, but rather they cause human disease and are found frequently in exome sequencing studies because of their genetic dominance and dosage sensitivity.
