Intrastrand base-stacking buttresses widening of major groovein interstrand cross-linked B-DNA

Mateus Webba da Silva, RG Bierbryer, CJ Wilds, AM Noronha, PS Miller, MP Gamcsik

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The introduction of a covalent interstrand cross-link induces changes in the intrinsic structure and deformability of theDNA helix that are recognized by elements of the DNA repair apparatus. In this context, the solution structure of the undecamerd(CGAAAT*TTTCG)2, where T* represents a N3T–butyl–N3T interstrand cross-link, was determined using molecular dynamicscalculations restrained by NOE and dihedral angle data obtained from NMR spectroscopy. The structure of this cross-linked undecamershows dramatic widening of the major groove of the B-DNA stem without disruption of Watson–Crick base pairing. Thischange in tertiary structure illustrates the cumulative effect of cooperativity in intrastrand base stacking of an A-tract of three adenines.Further, it is the direct result from the imposition of geometric angular constraints by the cross-link chain on an ApT* andT*pT steps in the segment AAAT*T. The widening of the major groove is due to the dominant contribution of base stacking to thestability of the ApT compared to the TpT step suggesting that the latter is more deformable within a DNA stem. Compared to earlierstructures of ethyl cross-linked oligonucleotides, this unique perturbation induced by the butyl moiety offers a new probe forsystematic studies of DNA repair mechanisms.
LanguageEnglish
JournalBIOORGANIC & MEDICINAL CHEMISTRY
Volume13
DOIs
Publication statusPublished - 9 Apr 2005

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B-Form DNA
DNA
Repair
Adenine
Dihedral angle
Formability
Oligonucleotides
Nuclear magnetic resonance spectroscopy

Cite this

Webba da Silva, Mateus ; Bierbryer, RG ; Wilds, CJ ; Noronha, AM ; Miller, PS ; Gamcsik, MP. / Intrastrand base-stacking buttresses widening of major groovein interstrand cross-linked B-DNA. 2005 ; Vol. 13.
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Intrastrand base-stacking buttresses widening of major groovein interstrand cross-linked B-DNA. / Webba da Silva, Mateus; Bierbryer, RG; Wilds, CJ; Noronha, AM; Miller, PS; Gamcsik, MP.

Vol. 13, 09.04.2005.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intrastrand base-stacking buttresses widening of major groovein interstrand cross-linked B-DNA

AU - Webba da Silva, Mateus

AU - Bierbryer, RG

AU - Wilds, CJ

AU - Noronha, AM

AU - Miller, PS

AU - Gamcsik, MP

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Y1 - 2005/4/9

N2 - The introduction of a covalent interstrand cross-link induces changes in the intrinsic structure and deformability of theDNA helix that are recognized by elements of the DNA repair apparatus. In this context, the solution structure of the undecamerd(CGAAAT*TTTCG)2, where T* represents a N3T–butyl–N3T interstrand cross-link, was determined using molecular dynamicscalculations restrained by NOE and dihedral angle data obtained from NMR spectroscopy. The structure of this cross-linked undecamershows dramatic widening of the major groove of the B-DNA stem without disruption of Watson–Crick base pairing. Thischange in tertiary structure illustrates the cumulative effect of cooperativity in intrastrand base stacking of an A-tract of three adenines.Further, it is the direct result from the imposition of geometric angular constraints by the cross-link chain on an ApT* andT*pT steps in the segment AAAT*T. The widening of the major groove is due to the dominant contribution of base stacking to thestability of the ApT compared to the TpT step suggesting that the latter is more deformable within a DNA stem. Compared to earlierstructures of ethyl cross-linked oligonucleotides, this unique perturbation induced by the butyl moiety offers a new probe forsystematic studies of DNA repair mechanisms.

AB - The introduction of a covalent interstrand cross-link induces changes in the intrinsic structure and deformability of theDNA helix that are recognized by elements of the DNA repair apparatus. In this context, the solution structure of the undecamerd(CGAAAT*TTTCG)2, where T* represents a N3T–butyl–N3T interstrand cross-link, was determined using molecular dynamicscalculations restrained by NOE and dihedral angle data obtained from NMR spectroscopy. The structure of this cross-linked undecamershows dramatic widening of the major groove of the B-DNA stem without disruption of Watson–Crick base pairing. Thischange in tertiary structure illustrates the cumulative effect of cooperativity in intrastrand base stacking of an A-tract of three adenines.Further, it is the direct result from the imposition of geometric angular constraints by the cross-link chain on an ApT* andT*pT steps in the segment AAAT*T. The widening of the major groove is due to the dominant contribution of base stacking to thestability of the ApT compared to the TpT step suggesting that the latter is more deformable within a DNA stem. Compared to earlierstructures of ethyl cross-linked oligonucleotides, this unique perturbation induced by the butyl moiety offers a new probe forsystematic studies of DNA repair mechanisms.

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