Swi2/Snf2 remodelers: hybrid views on hybrid molecular machines

Hopfner, Karl‐Peter; Gerhold, Christian-Benedikt; Lakomek, K.; Wollmann, Petra

doi:10.1016/j.sbi.2012.02.007

Cited by 65 publications

(66 citation statements)

References 53 publications

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“…SNF2-family proteins are required for efficient homologous recombination in eukaryotes (Flaus et al 2006;Ceballos and Heyer 2011;Hopfner et al 2012). In N. crassa, MUS-25 and at least three other SNF2-family proteins have been implicated in homologous recombination (Handa et al 2000;Zhang et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…This variability may be related to the aberrant meiosis and low fertility of heterozygous mus-25 + /mus-25 D crosses. While we have not investigated a mus-25 D sad-6 D mutant, it seems likely that such a strain would not be more fertile than the mus-25 D single mutant.SNF2-family proteins are required for efficient homologous recombination in eukaryotes (Flaus et al 2006;Ceballos and Heyer 2011;Hopfner et al 2012). In N. crassa, MUS-25 and at least three other SNF2-family proteins have been implicated in homologous recombination (Handa et al 2000;Zhang et al 2013).…”

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Efficient Detection of Unpaired DNA Requires a Member of the Rad54-Like Family of Homologous Recombination Proteins

et al. 2014

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Meiotic silencing by unpaired DNA (MSUD) is a process that detects unpaired regions between homologous chromosomes and silences them for the duration of sexual development. While the phenomenon of MSUD is well recognized, the process that detects unpaired DNA is poorly understood. In this report, we provide two lines of evidence linking unpaired DNA detection to a physical search for DNA homology. First, we have found that a putative SNF2-family protein (SAD-6) is required for efficient MSUD in Neurospora crassa. SAD-6 is closely related to Rad54, a protein known to facilitate key steps in the repair of double-strand breaks by homologous recombination. Second, we have successfully masked unpaired DNA by placing identical transgenes at slightly different locations on homologous chromosomes. This masking falls apart when the distance between the transgenes is increased. We propose a model where unpaired DNA detection during MSUD is achieved through a spatially constrained search for DNA homology. The identity of SAD-6 as a Rad54 paralog suggests that this process may be similar to the searching mechanism used during homologous recombination. MEIOSIS is fundamental to sexual reproduction. During meiosis, chromosomes are replicated, aligned, recombined, and segregated to nuclei that will develop into gametes. Two of these key processes, alignment and recombination, likely require a search for DNA homology between chromosomes (Barzel and Kupiec 2008;Moore and Shaw 2009). Such homology searching is necessary because sexual organisms inherit a copy of each chromosome from each of its parents. These chromosomes, referred to as homologs, must somehow find each other so that alignment, recombination, and segregation can occur.Although recent research has improved our understanding of homology search mechanisms (Forget and Kowalczykowski 2012;Renkawitz et al. 2013), there are many questions that remain unanswered. The filamentous fungus Neurospora crassa may be useful for investigating the unknowns of homology searching because it possesses a genetically tractable phenomenon called meiotic silencing by unpaired DNA (MSUD) (Aramayo and Selker 2013;Billmyre et al. 2013). MSUD scans pairs of homologs for segments of DNA that are not accurately paired between them. If improper pairing (i.e., unpairing) is identified, the offending sequences are silenced for the duration of sexual development. For example, if a hypothetical gene called "gene A" is on the left arm of one chromosome but on the right arm of its homolog, it will be silenced. The same holds true if gene A has been lost from one of the homologs.A functional MSUD response can be easily detected with alleles that affect ascospore (sexual spore) color or shape. Indeed, MSUD was discovered during studies of ascospore maturation-1 (asm-1), a gene required for the production of pigmented (black) ascospores . A cross between an asm-1 + strain and an asm-1 D strain produces mostly unpigmented (white) ascospores. This is because MSUD silences the unpaired asm-1 + all...

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Section: Discussionmentioning

confidence: 99%

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Efficient Detection of Unpaired DNA Requires a Member of the Rad54-Like Family of Homologous Recombination Proteins

et al. 2014

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“…They are grouped into different classes with unique features and specificity ( Fig. 2) and are able to recognize a plethora of chromatin marks, either through diverse protein domains and/or through interaction with a large set of different subunits (Hopfner et al, 2012). This complexity reflects the multiple functions of remodelers in DNA-related processes, and it is not surprising that mutants lacking functional chromatin remodelers often exhibit increased sensitivity to DNA damage.…”

Section: Chromatin-remodeling Complexes Connected With Ddrmentioning

confidence: 99%

DNA Damage Repair in the Context of Plant Chromatin

Donà

Scheid

2015

Plant Physiol.

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The integrity of DNA molecules is constantly challenged. All organisms have developed mechanisms to detect and repair multiple types of DNA lesions. The basic principles of DNA damage repair (DDR) in prokaryotes and unicellular and multicellular eukaryotes are similar, but the association of DNA with nucleosomes in eukaryotic chromatin requires mechanisms that allow access of repair enzymes to the lesions. This is achieved by chromatin-remodeling factors, and their necessity for efficient DDR has recently been demonstrated for several organisms and repair pathways. Plants share many features of chromatin organization and DNA repair with fungi and animals, but they differ in other, important details, which are both interesting and relevant for our understanding of genome stability and genetic diversity. In this Update, we compare the knowledge of the role of chromatin and chromatin-modifying factors during DDR in plants with equivalent systems in yeast and humans. We emphasize plant-specific elements and discuss possible implications.A DNA molecule in a eukaryotic chromosome has a diameter of 2 nm but a length in the range of centimeters. Being 10 7 times longer than it is wide would make it highly sensitive to breakage if it were not organized in compact and dynamic chromatin, with nucleosomes as basic units followed by multiple higher order levels of organization. Within this packaging, replication and transcription constitute an endogenous mechanical strain, while exposure of cells to physical or chemical hazard creates a wide range of DNA damage induced by external factors, including photoproducts, pyrimidine dimers, interstrand crosslinking, and single and double-strand breaks (DSBs). All organisms possess mechanisms that repair DNA molecules. DNA damage repair (DDR) systems for the various types of damage are overlapping as well as complementary, and their prevalence depends on the organism, the stage of the cell cycle, the site and the amount of damage, and the availability of intact templates. A coarse categorization distinguishes nucleotide excision repair, base excision repair, nonhomologous end joining (NHEJ), and homologous recombination (HR). Many schematic models for these DDR pathways describe the action and interaction of several repair components, but they are usually misleading in one aspect: DNA strands are illustrated as straight lines, neglecting the emerging role of chromatin for the location and the fate of DNA lesions. More realistically, we should envisage DNA lesions in the chromatin context like the leakage or burst of an in-ground pipe. Recognizing the defect, localizing it, excavating the broken parts, cleaning the ends, reconnecting them, and restoring the original state are mirrored in the subsequent steps of DDR: signaling, labeling, accessing, resecting, religating, and reassembling. Chromatin is expected to especially affect the access, resection, and restoration of the original arrangement, and several factors that can dissolve higher order structures, slide, evict, or exchange ...

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“…The C-terminal region of Mot1, which comprises the ATPase domain, interacts with DNA upstream of the TATA box (13,14). Given the sequence and structural similarity among Snf2/Swi2 ATPase domains (15,16), a central goal in the field has been to decipher the mechanisms by which these enzymes couple ATP hydrolysis to dissociation or rearrangement of protein-DNA complexes.…”

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confidence: 99%

Molecular Mechanism of Mot1, a TATA-binding Protein (TBP)-DNA Dissociating Enzyme

Viswanathan

True

Auble

2016

Journal of Biological Chemistry

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The essential Saccharomyces cerevisiae ATPase Mot1 globally regulates transcription by impacting the genomic distribution and activity of the TATA-binding protein (TBP). In vitro, Mot1 forms a ternary complex with TBP and DNA and can use ATP hydrolysis to dissociate the TBP-DNA complex. Prior work suggested an interaction between the ATPase domain and a functionally important segment of DNA flanking the TATA sequence. However, how ATP hydrolysis facilitates removal of TBP from DNA is not well understood, and several models have been proposed. To gain insight into the Mot1 mechanism, we dissected the role of the flanking DNA segment by biochemical analysis of complexes formed using DNAs with short singlestranded gaps. In parallel, we used a DNA tethered cleavage approach to map regions of Mot1 in proximity to the DNA under different conditions. Our results define non-equivalent roles for bases within a broad segment of flanking DNA required for Mot1 action. Moreover, we present biochemical evidence for two distinct conformations of the Mot1 ATPase, the detection of which can be modulated by ATP analogs as well as DNA sequence flanking the TATA sequence. We also show using purified complexes that Mot1 dissociation of a stable, high affinity TBP-DNA interaction is surprisingly inefficient, suggesting how other transcription factors that bind to TBP may compete with Mot1. Taken together, these results suggest that TBP-DNA affinity as well as other aspects of promoter sequence influence Mot1 function in vivo.Snf2/Swi2 enzymes play critical roles in regulation of essentially all DNA metabolic processes by utilizing the energy of ATP hydrolysis to alter protein-DNA interactions (1-4). Mot1, 2 a Snf2/Swi2 protein, dissociates the TATA-binding protein (TBP) from promoters and thereby regulates TBP distribution in the cell (5-9). By exploiting the Mot1 experimental system, biochemical analyses of the TBP-DNA dissociation reaction have provided general insight into mechanisms by which Snf2/Swi2 ATPases catalyze rearrangements of stable protein-DNA complexes (4). The N terminus of Mot1 interacts with TBP through its flexible HEAT repeats and in this way recruits Mot1 to TBP-DNA (7, 10 -14). The C-terminal region of Mot1, which comprises the ATPase domain, interacts with DNA upstream of the TATA box (13,14). Given the sequence and structural similarity among Snf2/Swi2 ATPase domains (15, 16), a central goal in the field has been to decipher the mechanisms by which these enzymes couple ATP hydrolysis to dissociation or rearrangement of protein-DNA complexes.The Snf2/Swi2 ATPases comprise a group within the SF2 helicase superfamily (17). Thus, their mechanisms are proposed to be similar to those of helicases except that they do not catalyze DNA strand separation (15,18). Nonetheless, the Snf2/ Swi2 family has well over a thousand members, and the great majority of them have not been characterized biochemically (19). Biochemical studies of helicases have revealed diverse mechanistic properties (3), suggesting that Snf2/Swi2 enz...

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Swi2/Snf2 remodelers: hybrid views on hybrid molecular machines

Cited by 65 publications

References 53 publications

Efficient Detection of Unpaired DNA Requires a Member of the Rad54-Like Family of Homologous Recombination Proteins

Efficient Detection of Unpaired DNA Requires a Member of the Rad54-Like Family of Homologous Recombination Proteins

DNA Damage Repair in the Context of Plant Chromatin

Molecular Mechanism of Mot1, a TATA-binding Protein (TBP)-DNA Dissociating Enzyme

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