Chemical nucleases

Sigman, David S.

doi:10.1021/bi00491a001

Cited by 301 publications

(236 citation statements)

References 90 publications

Supporting

Mentioning

230

Contrasting

Order By: Relevance

“…5-Phenyl-1,10-phenanthroline-Cu cleaves DNA by binding to the minor groove and forming a copper-oxygen species, therefore it is sensitive to changes in minor groove geometry (47). Hypersensitivity to 5-phenyl-OP-Cu cleavage was visible only with ZntR, Zn(II), and RNAP together (Fig.…”

Section: Zntr Purification and Metal Content-mentioning

confidence: 97%

DNA Distortion Mechanism for Transcriptional Activation by ZntR, a Zn(II)-responsive MerR Homologue in Escherichia coli

Outten¹,

Outten²,

O’Halloran³

1999

Journal of Biological Chemistry

185

198

View full text Add to dashboard Cite

MerR-like DNA distortion mechanisms have been proposed for a variety of stress-responsive transcription factors. The Escherichia coli ZntR protein, a homologue of MerR, has recently been shown to mediate Zn(II)-responsive regulation of zntA, a gene involved in Zn(II) detoxification. To determine whether the MerR DNA distortion mechanism is conserved among MerR family members, we have purified ZntR to homogeneity and shown that it is a zinc receptor that is necessary and sufficient to stimulate Zn-responsive transcription at the zntA promoter. Biochemical, DNA footprinting, and in vitro transcription assays indicate that apo-ZntR binds in the atypical 20-base pair spacer region of the promoter and distorts the DNA in a manner that is similar to apo-MerR. The addition of Zn(II) to ZntR converts it to a transcriptional activator protein that introduces changes in the DNA conformation. These changes apparently make the promoter a better substrate for RNA polymerase. We propose that this zinc-sensing homologue of MerR restructures the target promoter in a manner similar to that of other stress-responsive transcription factors. The ZntR metalloregulatory protein is a direct Zn(II) sensor that catalyzes transcriptional activation of a zinc efflux gene, thus preventing intracellular Zn(II) from exceeding an optimal but as yet unknown concentration.

show abstract

Section: Zntr Purification and Metal Content-mentioning

confidence: 97%

DNA Distortion Mechanism for Transcriptional Activation by ZntR, a Zn(II)-responsive MerR Homologue in Escherichia coli

Outten¹,

Outten²,

O’Halloran³

1999

Journal of Biological Chemistry

185

198

View full text Add to dashboard Cite

show abstract

“…The Cu(phen) 2 complex is a small (∼13 Å and 460 Da), structure-specific, sequenceindependent probe that cleaves distortions in RNA helices (32)(33)(34) including the ferritin IRE (18,19,35).…”

Section: Effects Of Internal Loop/bulge and Hairpin Loop Mutations Onmentioning

confidence: 99%

Internal Loop/Bulge and Hairpin Loop of the Iron-Responsive Element of Ferritin mRNA Contribute to Maximal Iron Regulatory Protein 2 Binding and Translational Regulation in the Iso-iron-responsive Element/Iso-iron Regulatory Protein Family

Sierzputowska-Gracz

Gdaniec

et al. 2000

Biochemistry

View full text Add to dashboard Cite

Iron-responsive elements (IREs), a natural group of mRNA-specific sequences, bind iron regulatory proteins (IRPs) differentially and fold into hairpins [with a hexaloop (HL) CAGUGX] with helical distortions: an internal loop/bulge (IL/B) (UGC/C) or C-bulge. C-bulge iso-IREs bind IRP2 more poorly, as oligomers (n ) 28-30), and have a weaker signal response in vivo. Two trans-loop GC base pairs occur in the ferritin IRE (IL/B and HL) but only one in C-bulge iso-IREs (HL); metal ions and protons perturb the IL/B [Gdaniec et al. (1998) Biochemistry 37, 1505-1512. IRE function (translation) and physical properties (T m and accessibility to nucleases) are now compared for IL/B and C-bulge IREs and for HL mutants. Conversion of the IL/B into a C-bulge by a single deletion in the IL/B or by substituting the HL CG base pair with UA both derepressed ferritin synthesis 4-fold in rabbit reticulocyte lysates (IRP1 + IRP2), confirming differences in IRP2 binding observed for the oligomers. Since the engineered C-bulge IRE was more helical near the IL/B [Cu(phen) 2 resistant] and more stable (T m increased) and the HL mutant was less helical near the IL/B (ribonuclease T1 sensitive) and less stable (T m decreased), both CG trans-loop base pairs contribute to maximum IRP2 binding and translational regulation. The 1 H NMR spectrum of the Mg-IRE complex revealed, in contrast to the localized IL/B effects of Co(III) hexaammine observed previously, perturbation of the IL/B plus HL and interloop helix. The lower stability and greater helix distortion in the ferritin IL/B-IRE compared to the C-bulge iso-IREs create a combinatorial set of RNA/protein interactions that control protein synthesis rates with a range of signal sensitivities.Awareness of mRNA regulation as a mechanism for controlling gene expression is increasing. The iso-IRE (iron responsive element) 1 family of mRNA regulatory elements recognized by the cognate proteins, iron regulatory proteins (IRPs), is one of the most extensively characterized mRNA regulatory targets. However, knowledge about mRNA regulation is in its infancy compared to understanding of DNA regulation such as hormone response elements recognized by hormone nuclear receptors (1). The ancient nature of the proteins encoded in IRE-containing, animal mRNAs (e.g., aconitase, ferritin), the homology of the IRPs to aconitases, and the recent detection of functional IREs and IRPs in bacteria (2) as well as animals suggest that the IRE/IRP interaction is also ancient, possibly representing regulation in an RNA world.The common structural features of iso-IREs are a hairpin hexaloop (CAGUGX) with a trans-loop GC base pair and a helical stem (3-5). The GC base pair in the hexaloop has a large effect on the stabilization of the overall IRE structure (3,6). A disordered C residue occurs in all IREs (4, 5). In many iso-IREs, the disordered C is a bulge in the helix of the IRE stem (4). In another type of iso-IRE, the disordered C residue is part of a set of four conserved residues [UGC-(16 nucleotides)-C]...

show abstract

“…The characterization of DNA recognition by small redox-or photoactive transition metal complexes has been substantially aided by studying the DNA cleavage activity [5][6][7][8]. Double-strand breaks in duplex DNA are thought to be more significant sources of cell lethality than are single strand breaks, as they appear to be less readily repaired by DNA repair mechanisms [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Selvakumar

Rajendiran

Maheswari

et al. 2006

Journal of Inorganic Biochemistry

290

140

View full text Add to dashboard Cite

Chemical nucleases

Cited by 301 publications

References 90 publications

DNA Distortion Mechanism for Transcriptional Activation by ZntR, a Zn(II)-responsive MerR Homologue in Escherichia coli

DNA Distortion Mechanism for Transcriptional Activation by ZntR, a Zn(II)-responsive MerR Homologue in Escherichia coli

Internal Loop/Bulge and Hairpin Loop of the Iron-Responsive Element of Ferritin mRNA Contribute to Maximal Iron Regulatory Protein 2 Binding and Translational Regulation in the Iso-iron-responsive Element/Iso-iron Regulatory Protein Family

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

Contact Info

Product

Resources

About