Structure of a Psoralen Cross-Linked DNA in Solution by Nuclear Magnetic Resonance

Tomić, Milan; Wemmer, David E.; Kim, Sung‐Hou

doi:10.1126/science.3686011

Cited by 70 publications

(54 citation statements)

References 31 publications

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“…Thymines in 5Ј-TpA sites of B-form duplex DNA are the preferential targets of psoralens (63,64). As judged by NMR analysis, interstrand psoralen cross-links distort the double helix of B-form DNA only slightly (65). Consistent with this conclusion, we observed that TBP was able to bind to the cross-linked substrate we prepared as efficiently as to an identical, but non-cross-linked, probe (Fig.…”

Section: Figsupporting

confidence: 77%

Purification and Enzymic Properties of Mot1 ATPase, a Regulator of Basal Transcription in the Yeast Saccharomyces cerevisiae

Adamkewicz

Mueller²,

Hansen

et al. 2000

Journal of Biological Chemistry

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The 1867-residue Mot1 protein is a member of a superfamily of ATPases, some of which are helicases, that interact with protein-nucleic acid assemblies. Mot1 is an essential regulator of RNA polymerase II-dependent transcription in vivo and dissociates TATA box-binding protein (TBP)-DNA complexes in vitro. Mot1-(His) 6 was purified to apparent homogeneity from yeast extracts. The preparation efficiently dissociated TBP⅐TATA complexes, suggesting that no other protein or cofactor is required. Mot1 behaved as a non-globular monomer in hydrodynamic studies, and no association was detected between differentially tagged co-expressed Mot1 constructs. ATPase activity was stimulated Transcription by all three eukaryotic RNA polymerases requires TBP.1 For initiation by yeast Pol II, TBP binding to a TATA sequence present in most promoters nucleates stepwise assembly of a large complex containing TBP-associated factors (1), termed TFIID, as well as multiple general transcription factors and Pol II (reviewed in Refs. 2-5). In an alternative, but not mutually exclusive, model of initiation, TFIID binding creates a platform for recruitment of a massive holoenzyme, consisting of Pol II, the SRB proteins, and other cofactors (like Gal11), as well as the general transcription factors, TFIIB, TFIIF, and TFIIH (reviewed in Refs. 6 -8). In both models, promoter binding by TBP is the rate-limiting step in initiation complex formation and thus provides a physiologically relevant target for transcriptional control by both positive (9, 10) and negative (11-14) regulatory factors.Factors that negatively regulate eukaryotic transcription utilize a wide variety of mechanisms, including quenching of activators, promoting assembly of chromatin, recruiting chromatin-binding proteins or histone-modifying enzymes, and interfering with the general transcription machinery itself. In addition, several proteins are thought to block Pol II transcription via interaction with TBP. Such regulators include Evenskipped (eve gene product), a Drosophila homeodomain protein (15, 16), and a general repressor, NC2 (or Dr1-DRAP1) (17-19). NC2 binds to TBP⅐DNA complexes and prevents the association of TFIIA and TFIIB, possibly by altering conformation of the .Another kind of negative regulator of TBP action was first identified both genetically and biochemically in the yeast Saccharomyces cerevisiae. A TBP-targeted repressing activity, termed ADI for "ATP-dependent inhibitor" of TATA binding, was detected in yeast nuclear extracts (25). ADI removed TBP from the TATA element of the adenovirus major late promoter (AdMLP) in an ATP-dependent manner. TFIIA, and to some extent TFIIB, inhibited ADI activity by competing for binding to TBP or by stabilizing the TBP⅐DNA complex, or both (25). It was subsequently found that ADI corresponded to the product of the MOT1 gene (26). The MOT1 locus had been previously identified by temperature-sensitive mutations that increased basal expression of many Pol II-specific genes (27, 28).The MOT1 gene was isolated by complementat...

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Section: Figsupporting

confidence: 77%

Purification and Enzymic Properties of Mot1 ATPase, a Regulator of Basal Transcription in the Yeast Saccharomyces cerevisiae

Adamkewicz

Mueller²,

Hansen

et al. 2000

Journal of Biological Chemistry

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show abstract

“…roughly parallel to each other and to the plane of psoralen, while the modified thymines undergo important angular deformations, especially TI which is situated at the extremity. No unwinding perturbation is observed, as opposed to the results obtained by Tomic et al, also from NMR data (27). This is probably due to the location of psoralen at the extremity of the oligonucleotide in our case.…”

Section: Location Of the Psoralen Derivativecontrasting

confidence: 56%

“…As already reported (27), the covalent photo-addition of psoralen across the 5-6 double bonds of thymines 1 and 2 shifts the H6 resonances into the same region as H4', H5' and H5" resonances of sugars (Fig. 4 and Table 2).…”

Section: Location Of the Psoralen Derivativesupporting

confidence: 55%

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Solution structure of oligonucleotides covalently linked to a psoralen derivative

et al. 1995

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maps, revealed that the mini double helix adopts a B-form conformation and that the deoxyriboses preferentially adopt a C2'-endo conformation. The nOe connectivities observed between the protons of the bases or the sugars In each duplex, and the protons of the psoralen and the hexamethylene chain, led us to propose a model involving an equilibrium between two conformations due to different locations of the psoralen. Upon UV-irradiation, the psoralen moiety crosslinked the two DNA strands at the level of 5'TpA3' sequences. NMR studies of the single major photocross-linked duplex pso-m6-d(TAAGCCG) and d(CGG-CTTA) were performed. The stereochemistry of the diadduct is indeed cis-syn at both cyclobutane rings. In addition, the effects of this diadduct on the helical structure are analyzed In detail.

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“…[69][70][71][72] However, a kink is neither a sufficient nor a necessary determinant for damage recognition, 67,68 and destabilization of the base-stacking interactions in the vicinity of the altered site has been singled out as the common feature of all DNA modifications that are recognized as damage by the excinuclease repair machinery. 68 The nature of this destabilization in ditercalinium-and Flexi-Di-DNA complexes has already been discussed.…”

Section: Discussionmentioning

confidence: 99%

Molecular Dynamics Simulations of the Bis-Intercalated Complexes of Ditercalinium and Flexi-Di with the Hexanucleotide d(GCGCGC)₂: Theoretical Analysis of the Interaction and Rationale for the Sequence Binding Specificity

et al. 1996

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The X-ray crystal structures of the complexes of ditercalinium and Flexi-Di with d(CGCG) 2 have been studied by computational chemistry methods in an attempt to rationalize their distinct structural features. In addition, the complexes of these two bisintercalating drugs with d(GCGCGC) 2 have been modeled and subjected to 0.5 ns of molecular dynamics simulations in explicit solvent with the aim of evaluating the relative importance of hydrogen bonding and stacking interactions in the sequence binding specificity of these compounds. According to our calculations, the electrostatic term is attractive for the stacking interactions between the pyridocarbazole chromophores of these drugs and the base pairs that make up the sandwiched GpC step. On the contrary, this energy term is repulsive for the base pairs that make up the boundaries of the bisintercalation site. This differential electrostatic binding energy component, which is shown to have a strong orientational dependence, could lie at the origin of the observed binding preferences of these drugs. In addition, both the Lennard-Jones and the electrostatic energy terms contribute to stabilizing the underwound central GpC step. The attractive electrostatic interactions between the linkers and the major groove are in concert with the stacking specificities for the sandwiched GpC step, which is thus very effectively stapled by the drugs. The hydrogen-bonding potential of the linkers, however, appears to be reduced in an aqueous medium due to competing interactions with water. Binding of either ditercalinium or Flexi-Di to d(GCGCGC) 2 appears to favor the A-type conformation that this DNA molecule most likely adopts in the free state. The possible relevance of these findings to the process of bis-intercalation and to the pharmacological action of these compounds is discussed.

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Structure of a Psoralen Cross-Linked DNA in Solution by Nuclear Magnetic Resonance

Cited by 70 publications

References 31 publications

Purification and Enzymic Properties of Mot1 ATPase, a Regulator of Basal Transcription in the Yeast Saccharomyces cerevisiae

Purification and Enzymic Properties of Mot1 ATPase, a Regulator of Basal Transcription in the Yeast Saccharomyces cerevisiae

Solution structure of oligonucleotides covalently linked to a psoralen derivative

Molecular Dynamics Simulations of the Bis-Intercalated Complexes of Ditercalinium and Flexi-Di with the Hexanucleotide d(GCGCGC)₂: Theoretical Analysis of the Interaction and Rationale for the Sequence Binding Specificity

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Structure of a Psoralen Cross-Linked DNA in Solution by Nuclear Magnetic Resonance

Cited by 70 publications

References 31 publications

Purification and Enzymic Properties of Mot1 ATPase, a Regulator of Basal Transcription in the Yeast Saccharomyces cerevisiae

Purification and Enzymic Properties of Mot1 ATPase, a Regulator of Basal Transcription in the Yeast Saccharomyces cerevisiae

Solution structure of oligonucleotides covalently linked to a psoralen derivative

Molecular Dynamics Simulations of the Bis-Intercalated Complexes of Ditercalinium and Flexi-Di with the Hexanucleotide d(GCGCGC)2: Theoretical Analysis of the Interaction and Rationale for the Sequence Binding Specificity

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Molecular Dynamics Simulations of the Bis-Intercalated Complexes of Ditercalinium and Flexi-Di with the Hexanucleotide d(GCGCGC)₂: Theoretical Analysis of the Interaction and Rationale for the Sequence Binding Specificity