The conserved histone variant H2AZ has an important role in the regulation of gene expression and the establishment of a buffer to the spread of silent heterochromatin. How histone variants such as H2AZ are incorporated into nucleosomes has been obscure. We have found that Swr1, a Swi2/Snf2-related adenosine triphosphatase, is the catalytic core of a multisubunit, histone-variant exchanger that efficiently replaces conventional histone H2A with histone H2AZ in nucleosome arrays. Swr1 is required for the deposition of histone H2AZ at specific chromosome locations in vivo, and Swr1 and H2AZ commonly regulate a subset of yeast genes. These findings define a previously unknown role for the adenosine triphosphate–dependent chromatin remodeling machinery.

The mismatch repair pathway in Escherichia coli has been extensively studied in vitro as well as in vivo. The molecular mechanisms by which nucleotide cofactors regulate the whole process constitute an area of active debate. Here we demonstrate that nucleotide (ADP or ATP) binding to MutS mediates a switch in protein conformation. However, in MutS that is DNA bound, this switch ensues only with ATP and not with ADP and is similar, irrespective of whether it is bound to a homo- or a heteroduplex. The results envisage a minimal model of three confor­mational states of MutS as reflected in: (i) a specific and highly stable MutS–mismatch complex in the absence of a nucleotide; (ii) a specific but less stable complex in the presence of ATP hydrolysis; and (iii) an irreversibly dissociated complex in the presence of ATP binding (ATPγS). Such transitions are of relevance to the protein’s function in vivo where it has to first recognize a mismatch, followed by a search for hemimethylated sites.