Accommodation of Mispair Aligned N3T-Ethyl-N3T DNA Interstrand Cross Link

Mateus Webba da Silva, CJ Wilds, AM Noronha, OM Colvin, PS Miller, MP Gamcsik

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The solution structure of the undecamer d(CGAAAT*TTTCG)2, where T* represents a N3Tethyl-N3T interstrand cross link, was elucidated using molecular dynamics calculations restrained by NOEand dihedral data obtained from NMR spectroscopy. The ethyl moiety is particularly well-accommodatedbetween the minor and major grooves. This is an exceptional example of the plasticity along the axisdefined by the stem and a unique finding of an interstrand cross link occupying the area associatingminor and major grooves. The mismatch-aligned tethered bases preserve good intrastrand stacking withflanking bases. Base-pair steps adjacent to the lesion site are overwound. Accommodation of the lesionalso results in an increase in mispair staggering alignment modulated by flexibility because of the tetrahedralgeometry of the exocyclic ethyl carbon atoms. This is mechanically coupled with a small measure ofconcomitant propeller twisting without an increase in intrastrand base-step distance. Both x displacementand sugar puckering are indicative of canonical B DNA throughout the stem. We have thus establishedthat the lesion defined by mismatch-aligned minor groove N3T-ethyl-N3T cross-linked thymine basesproduces very localized distortions in a DNA stem that may be difficult to recognize by repair mechanismsthat are not transcription- or replication-coupled. Thus, this synthetic DNA is a valuable structural probeto study mechanisms of repair.
LanguageEnglish
JournalBiochemistry
Volume43
DOIs
Publication statusPublished - 9 Aug 2004

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DNA
Repair
Thymine
Propellers
Molecular Dynamics Simulation
Transcription
Sugars
Base Pairing
Nuclear magnetic resonance spectroscopy
Plasticity
Molecular dynamics
Magnetic Resonance Spectroscopy
Carbon
Atoms

Cite this

Webba da Silva, Mateus ; Wilds, CJ ; Noronha, AM ; Colvin, OM ; Miller, PS ; Gamcsik, MP. / Accommodation of Mispair Aligned N3T-Ethyl-N3T DNA Interstrand Cross Link. In: Biochemistry. 2004 ; Vol. 43.
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abstract = "The solution structure of the undecamer d(CGAAAT*TTTCG)2, where T* represents a N3Tethyl-N3T interstrand cross link, was elucidated using molecular dynamics calculations restrained by NOEand dihedral data obtained from NMR spectroscopy. The ethyl moiety is particularly well-accommodatedbetween the minor and major grooves. This is an exceptional example of the plasticity along the axisdefined by the stem and a unique finding of an interstrand cross link occupying the area associatingminor and major grooves. The mismatch-aligned tethered bases preserve good intrastrand stacking withflanking bases. Base-pair steps adjacent to the lesion site are overwound. Accommodation of the lesionalso results in an increase in mispair staggering alignment modulated by flexibility because of the tetrahedralgeometry of the exocyclic ethyl carbon atoms. This is mechanically coupled with a small measure ofconcomitant propeller twisting without an increase in intrastrand base-step distance. Both x displacementand sugar puckering are indicative of canonical B DNA throughout the stem. We have thus establishedthat the lesion defined by mismatch-aligned minor groove N3T-ethyl-N3T cross-linked thymine basesproduces very localized distortions in a DNA stem that may be difficult to recognize by repair mechanismsthat are not transcription- or replication-coupled. Thus, this synthetic DNA is a valuable structural probeto study mechanisms of repair.",
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Accommodation of Mispair Aligned N3T-Ethyl-N3T DNA Interstrand Cross Link. / Webba da Silva, Mateus; Wilds, CJ; Noronha, AM; Colvin, OM; Miller, PS; Gamcsik, MP.

In: Biochemistry, Vol. 43, 09.08.2004.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Accommodation of Mispair Aligned N3T-Ethyl-N3T DNA Interstrand Cross Link

AU - Webba da Silva, Mateus

AU - Wilds, CJ

AU - Noronha, AM

AU - Colvin, OM

AU - Miller, PS

AU - Gamcsik, MP

PY - 2004/8/9

Y1 - 2004/8/9

N2 - The solution structure of the undecamer d(CGAAAT*TTTCG)2, where T* represents a N3Tethyl-N3T interstrand cross link, was elucidated using molecular dynamics calculations restrained by NOEand dihedral data obtained from NMR spectroscopy. The ethyl moiety is particularly well-accommodatedbetween the minor and major grooves. This is an exceptional example of the plasticity along the axisdefined by the stem and a unique finding of an interstrand cross link occupying the area associatingminor and major grooves. The mismatch-aligned tethered bases preserve good intrastrand stacking withflanking bases. Base-pair steps adjacent to the lesion site are overwound. Accommodation of the lesionalso results in an increase in mispair staggering alignment modulated by flexibility because of the tetrahedralgeometry of the exocyclic ethyl carbon atoms. This is mechanically coupled with a small measure ofconcomitant propeller twisting without an increase in intrastrand base-step distance. Both x displacementand sugar puckering are indicative of canonical B DNA throughout the stem. We have thus establishedthat the lesion defined by mismatch-aligned minor groove N3T-ethyl-N3T cross-linked thymine basesproduces very localized distortions in a DNA stem that may be difficult to recognize by repair mechanismsthat are not transcription- or replication-coupled. Thus, this synthetic DNA is a valuable structural probeto study mechanisms of repair.

AB - The solution structure of the undecamer d(CGAAAT*TTTCG)2, where T* represents a N3Tethyl-N3T interstrand cross link, was elucidated using molecular dynamics calculations restrained by NOEand dihedral data obtained from NMR spectroscopy. The ethyl moiety is particularly well-accommodatedbetween the minor and major grooves. This is an exceptional example of the plasticity along the axisdefined by the stem and a unique finding of an interstrand cross link occupying the area associatingminor and major grooves. The mismatch-aligned tethered bases preserve good intrastrand stacking withflanking bases. Base-pair steps adjacent to the lesion site are overwound. Accommodation of the lesionalso results in an increase in mispair staggering alignment modulated by flexibility because of the tetrahedralgeometry of the exocyclic ethyl carbon atoms. This is mechanically coupled with a small measure ofconcomitant propeller twisting without an increase in intrastrand base-step distance. Both x displacementand sugar puckering are indicative of canonical B DNA throughout the stem. We have thus establishedthat the lesion defined by mismatch-aligned minor groove N3T-ethyl-N3T cross-linked thymine basesproduces very localized distortions in a DNA stem that may be difficult to recognize by repair mechanismsthat are not transcription- or replication-coupled. Thus, this synthetic DNA is a valuable structural probeto study mechanisms of repair.

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