Forgot your password?
New user?
New Window Opens on the Secret Life of Microbes: Scientists Develop First Microbial Profiles of Ecosystems
CAS announces the release of SciFinder Scholar for Mac OS X
Press Releases
Press Releases
| Check out our New Publishers' Select for Free Articles |
BBA - Gene Regulatory Mechanisms (v.1809, #9)
Structure and function of RapA: A bacterial Swi2/Snf2 protein required for RNA polymerase recycling in transcription by Ding Jun Jin; Yan Ning Zhou; Gary Shaw; Xinhua Ji (pp. 470-475).
One of the hallmarks of the Swi2/Snf2 family members is their ability to modify the interaction between DNA-binding protein and DNA in controlling gene expression. The studies of Swi2/Snf2 have been mostly focused on their roles in chromatin and/or nucleosome remodeling in eukaryotes. A bacterial Swi2/Snf2 protein named RapA from Escherichia coli is a unique addition to these studies. RapA is anRNA polymerase (RNAP)-associatedprotein and anATPase. It binds nucleic acids including RNA and DNA. The ATPase activity of RapA is stimulated by its interaction with RNAP, but not with nucleic acids. RapA and the major sigma factor σ70 compete for binding to core RNAP. After one transcription cycle in vitro, RNAP is immobilized in an undefined posttranscription/posttermination complex (PTC), thus becoming unavailable for reuse. RapA stimulates RNAP recycling by ATPase-dependent remodeling of PTC, leading to the release of sequestered RNAP, which then becomes available for reuse in another cycle of transcription. Recently, the crystal structure of RapA that is also the first full-length structure for the entire Swi2/Snf2 family was determined. The structure provides a framework for future studies of the mechanism of RNAP recycling in transcription. This article is part of a Special Issue entitled: Snf2/Swi2 ATPase structure and function.► RapA in E. coli is so far the best characterized bacterial Swi2/Snf2. ► RapA is anRNA polymerase (RNAP)-associatedprotein and anATPase. ► RapA activates transcription by promoting RNAP release from a posttranscription/posttermination complex. ► The crystal structure of RapA provides a framework for future studies of the mechanism of RNAP recycling in transcription.
Keywords: RapA; Bacterial Swi2/Snf2; RNA polymerase recycling; Structure of Swi2/Snf2; Transcription complex remodeling
Diversity of operation in ATP-dependent chromatin remodelers by Swetansu K. Hota; Blaine Bartholomew (pp. 476-487).
Chromatin is actively restructured by a group of proteins that belong to the family of ATP-dependent DNA translocases. These chromatin remodelers can assemble, relocate or remove nucleosomes, the fundamental building blocks of chromatin. The family of ATP-dependent chromatin remodelers has many properties in common, but there are also important differences that may account for their varying roles in the cell. Some of the important characteristics of these complexes have begun to be revealed such as their interactions with chromatin and their mechanism of operation. The different domains of chromatin remodelers are discussed in terms of their targets and functional roles in mobilizing nucleosomes. The techniques that have driven these findings are discussed and how these have helped develop the current models for how nucleosomes are remodeled. This article is part of a Special Issue entitled: Snf2/Swi2 ATPase structure and function.► There are many different ATP-dependent chromatin remodelers each with their distinctive activity. ► Variations in remodeling activity are tied to how they interact with nucleosomes. ► Binding and remodeling are examined with bulk and single molecule techniques. ► ISWI type remodelers are sensitive to linker DNA length and space nucleosomes. ► The affinity, kinetic, and allosteric models of ISWI may explain how nucleosome spacing occurs. ► SWI/SNF type remodelers remove H2A-H2B dimers and disassemble nucleosomes in arrays.
Keywords: ATP-dependent chromatin remodeling; DNA helicase; ISWI; SWI/SNF; Nucleosome spacing; Nucleosome disassembly
One small step for Mot1; one giant leap for other Swi2/Snf2 enzymes? by Ramya Viswanathan; David T. Auble (pp. 488-496).
The TATA-binding protein (TBP) is a major target for transcriptional regulation. Mot1, a Swi2/Snf2-related ATPase, dissociates TBP from DNA in an ATP dependent process. The experimental advantages of this relatively simple reaction have been exploited to learn more about how Swi2/Snf2 ATPases function biochemically. However, many unanswered questions remain and fundamental aspects of the Mot1 mechanism are still under debate. Here, we review the available data and integrate the results with structural and biochemical studies of related enzymes to derive a model for Mot1's catalytic action consistent with the broad literature on enzymes in this family. We propose that the Mot1 ATPase domain is tethered to TBP by a flexible, spring-like linker of alpha helical hairpins. The linker juxtaposes the ATPase domain such that it can engage duplex DNA on one side of the TBP–DNA complex. This allows the ATPase to employ short-range, nonprocessive ATP-driven DNA tracking to pull or push TBP off its DNA site. DNA translocation is a conserved property of ATPases in the broader enzyme family. As such, the model explains how a structurally and functionally conserved ATPase domain has been put to use in a very different context than other enzymes in the Swi2/Snf2 family. This article is part of a Special Issue entitled:Snf2/Swi2 ATPase structure and function.► Different models for the Mot1 mechanism are discussed. ► A key aspect of the Mot1 mechanism is proposed to be DNA translocation, driven by an ATP-mediated conformational cycle. ► Rather than functioning as a simple tether, the spring-like nature of the Mot1 N-terminus is proposed to contribute to the catalytic mechanism. ► The Mot1 catalytic mechanism is proposed to be analogous to the initial ATP-driven steps in chromatin remodeling, arguing that mechanistic insights derived from analysis of Mot1 are applicable to other Swi2/Snf2 ATPases.
Keywords: TBP; Mot1; BTAF1; Swi2; Snf2; ATPase
Targeting chromatin remodelers: Signals and search mechanisms by Fabian Erdel; Jana Krug; Langst Gernot Längst; Karsten Rippe (pp. 497-508).
Chromatin remodeling complexes are ATP-driven molecular machines that change chromatin structure by translocating nucleosomes along the DNA, evicting nucleosomes, or changing the nucleosomal histone composition. They are highly abundant in the cell and numerous different complexes exist that display distinct activity patterns. Here we review chromatin-associated signals that are recognized by remodelers. It is discussed how these regulate the remodeling reaction via changing the nucleosome substrate/product binding affinity or the catalytic translocation rate. Finally, we address the question of how chromatin remodelers operate in the cell nucleus to find specifically marked nucleosome substrates via a diffusion driven target location mechanism, and estimate the search times of this process. This article is part of a Special Issue entitled:Snf2/Swi2 ATPase structure and function.► Summary of the most important chromatin signals recognized by remodelers. ► Reaction mechanism and key regulatory steps of remodeler activity. ► Review of signals that affect substrate binding or catalytic rate. ► Diffusion driven target location mechanisms of chromatin remodelers. > Search times for target identification in the cell nucleus.
Keywords: Chromatin remodeling; Nucleosome translocation; Histone modifications; Diffusion-controlled target location
Functions of the Snf2/Swi2 family Rad54 motor protein in homologous recombination by Shannon J. Ceballos; Wolf-Dietrich Heyer (pp. 509-523).
Homologous recombination is a central pathway to maintain genomic stability and is involved in the repair of DNA damage and replication fork support, as well as accurate chromosome segregation during meiosis. Rad54 is a dsDNA-dependent ATPase of the Snf2/Swi2 family of SF2 helicases, although Rad54 lacks classical helicase activity and cannot carry out the strand displacement reactions typical for DNA helicases. Rad54 is a potent and processive motor protein that translocates on dsDNA, potentially executing several functions in recombinational DNA repair. Rad54 acts in concert with Rad51, the central protein of recombination that performs the key reactions of homology search and DNA strand invasion. Here, we will review the role of the Rad54 protein in homologous recombination with an emphasis on mechanistic studies with the yeast and human enzymes. We will discuss how these results relate to in vivo functions of Rad54 during homologous recombination in somatic cells and during meiosis. This article is part of a Special Issue entitled: Snf2/Swi2 ATPase structure and function.► This review will focus on Rad54, its paralogs, and their function in recombination. ► Homologous recombination is a key pathway to maintain genomic integrity. ► Rad54 is a core component of the recombination machinery in all eukaryotes. ► The review focuses on mechanistic studies with the yeast and human enzymes. ► We relate the biochemical findings to genetic and cytological studies of Rad54.
Keywords: DNA repair; DNA replication; Genome stability; Homologous recombination; Meiosis; Motor protein