Disparity in the DNA translocase domains of SWI/SNF and ISW2

Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901-4413, USA.
Nucleic Acids Research (Impact Factor: 9.11). 01/2012; 40(10):4412-21. DOI: 10.1093/nar/gks007
Source: PubMed


An ATP-dependent DNA translocase domain consisting of seven conserved motifs is a general feature of all ATP-dependent chromatin
remodelers. While motifs on the ATPase domains of the yeast SWI/SNF and ISWI families of remodelers are highly conserved,
the ATPase domains of these complexes appear not to be functionally interchangeable. We found one reason that may account
for this is the ATPase domains interact differently with nucleosomes even though both associate with nucleosomal DNA 17–18 bp
from the dyad axis. The cleft formed between the two lobes of the ISW2 ATPase domain is bound to nucleosomal DNA and Isw2
associates with the side of nucleosomal DNA away from the histone octamer. The ATPase domain of SWI/SNF binds to the same
region of nucleosomal DNA, but is bound outside of the cleft region. The catalytic subunit of SWI/SNF also appears to intercalate
between the DNA gyre and histone octamer. The altered interactions of SWI/SNF with DNA are specific to nucleosomes and do
not occur with free DNA. These differences are likely mediated through interactions with the histone surface. The placement
of SWI/SNF between the octamer and DNA could make it easier to disrupt histone–DNA interactions.

Download full-text


Available from: Nilanjana Chatterjee
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The SWI/SNF chromatin remodeling complex changes the positions where nucleosomes are bound to DNA, exchanges out histone dimers, and disassembles nucleosomes. All of these activities depend on ATP hydrolysis by the catalytic subunit Snf2, containing a DNA-dependent ATPase domain. Here we examine the role of another domain in Snf2 called SnAC (Snf2 ATP coupling) that was shown previously to regulate the ATPase activity of SWI/SNF. We have found that SnAC has another function besides regulation of ATPase activity that is even more critical for nucleosome remodeling by SWI/SNF. We have found that deletion of the SnAC domain strongly uncouples ATP hydrolysis from nucleosome movement. Deletion of SnAC does not adversely affect the rate, processivity, or pulling force of SWI/SNF to translocate along free DNA in an ATP-dependent manner. The uncoupling of ATP hydrolysis from nucleosome movement is shown to be due to loss of SnAC binding to the histone surface of nucleosomes. While the SnAC domain targets both the ATPase domain and histones, the SnAC domain as a histone anchor plays a more critical role in remodeling because it is required to convert DNA translocation into nucleosome movement.
    Full-text · Article · Nov 2012 · Molecular and Cellular Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: ISWI slides nucleosomes along DNA, enabling the structural changes of chromatin required for the regulated use of eukaryotic genomes. Prominent mechanistic models imply cooperation of the ISWI ATPase domain with a C-terminal DNA-binding function residing in the HAND-SANT-SLIDE (HSS) domain. Contrary to these models, we show by quantitative biochemical means that all fundamental aspects of nucleosome remodeling are contained within the compact ATPase module of Drosophila ISWI. This domain can independently associate with DNA and nucleosomes, which in turn activate ATP turnover by inducing a conformational change in the enzyme, and it can autonomously reposition nucleosomes. The role of the HSS domain is to increase the affinity and specificity for nucleosomes. Nucleosome-remodeling enzymes may thus have evolved directly from ancestral helicase-type motors, and peripheral domains have furnished regulatory capabilities that bias the remodeling reaction toward different structural outcomes.
    No preview · Article · Dec 2012 · Nature Structural & Molecular Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Effective transcription, replication, and maintenance of the genome require a diverse set of molecular machines to perform the many chemical transactions that constitute these processes. Many of these machines use single-stranded nucleic acids as templates, and their actions are often regulated by the participation of nucleic acids in multimeric structures and macromolecular assemblies that restrict access to chemical information. Superfamily II (SF2) DNA helicases and translocases are a group of molecular machines that remodel nucleic acid lattices and enable essential cellular processes to use the information stored in the duplex DNA of the packaged genome. Characteristic accessory domains associated with the subgroups of the superfamily direct the activity of the common motor core and expand the repertoire of activities and substrates available to SF2 DNA helicases, translocases, and large multiprotein complexes containing SF2 motors. In recent years, single-molecule studies have contributed extensively to the characterization of this ubiquitous and essential class of enzymes.
    No preview · Article · Jan 2013 · Advances in Experimental Medicine and Biology
Show more