Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link

Mateus Webba Da Silva, Christopher J. Wilds, Anne M. Noronha, O. Michael Colvin, Paul S. Miller, Michael P. Gamcsik

Research output: Contribution to journalArticle

Abstract

The solution structure of the undecamer d(CGAAAT*TTTCG)2, where T* represents a N3T-ethyl-N3T interstrand cross link, was elucidated using molecular dynamics calculations restrained by NOE and dihedral data obtained from NMR spectroscopy. The ethyl moiety is particularly well-accommodated between the minor and major grooves. This is an exceptional example of the plasticity along the axis defined by the stem and a unique finding of an interstrand cross link occupying the area associating minor and major grooves. The mismatch-aligned tethered bases preserve good intrastrand stacking with flanking bases. Base-pair steps adjacent to the lesion site are overwound. Accommodation of the lesion also results in an increase in mispair staggering alignment modulated by flexibility because of the tetrahedral geometry of the exocyclic ethyl carbon atoms. This is mechanically coupled with a small measure of concomitant propeller twisting without an increase in intrastrand base-step distance. Both x displacement and sugar puckering are indicative of canonical B DNA throughout the stem. We have thus established that the lesion defined by mismatch-aligned minor groove N3T-ethyl-N 3T cross-linked thymine bases produces very localized distortions in a DNA stem that may be difficult to recognize by repair mechanisms that are not transcription- or replication-coupled. Thus, this synthetic DNA is a valuable structural probe to study mechanisms of repair.

Original languageEnglish (US)
Pages (from-to)12549-12554
Number of pages6
JournalBiochemistry®
Volume43
Issue number39
DOIs
StatePublished - Oct 5 2004

Fingerprint

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Webba Da Silva, M., Wilds, C. J., Noronha, A. M., Colvin, O. M., Miller, P. S., & Gamcsik, M. P. (2004). Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link. Biochemistry®, 43(39), 12549-12554. https://doi.org/10.1021/bi0486435

Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link. / Webba Da Silva, Mateus; Wilds, Christopher J.; Noronha, Anne M.; Colvin, O. Michael; Miller, Paul S.; Gamcsik, Michael P.

In: Biochemistry®, Vol. 43, No. 39, 05.10.2004, p. 12549-12554.

Research output: Contribution to journalArticle

Webba Da Silva, M, Wilds, CJ, Noronha, AM, Colvin, OM, Miller, PS & Gamcsik, MP 2004, 'Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link', Biochemistry®, vol. 43, no. 39, pp. 12549-12554. https://doi.org/10.1021/bi0486435
Webba Da Silva M, Wilds CJ, Noronha AM, Colvin OM, Miller PS, Gamcsik MP. Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link. Biochemistry®. 2004 Oct 5;43(39):12549-12554. https://doi.org/10.1021/bi0486435
Webba Da Silva, Mateus ; Wilds, Christopher J. ; Noronha, Anne M. ; Colvin, O. Michael ; Miller, Paul S. ; Gamcsik, Michael P. / Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link. In: Biochemistry®. 2004 ; Vol. 43, No. 39. pp. 12549-12554.
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