Backbone dynamics of DNA containing 8-oxoguanine

Importance for substrate recognition by base excision repair glycosylases

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Except for the functional groups sited within the major or minor grooves, the bases of B-DNA are quite protected from the external environment. Enzymes that modify the bases often "flip out" the target into an extrahelical position before the chemistry step is carried out. Examples of this mechanism are the base excision repair glycosylases and the restriction enzyme methylases. The question arises about the mechanism of substrate recognition for these enzymes and how closely it is linked to the base flipping step. Molecular dynamics simulations (AMBER, PME electrostatics) of fully solvated, cation neutralized, DNA sequences containing 8-oxoguanine (8OG) and of appropriate normal (control) DNAs have been carried out. The dynamics trajectories were analyzed to identify those properties of the DNA structure in the vicinity of the altered base, or its dynamics, that could contribute to molecular discrimination between substrate and non-substrate DNA sites. The results predict that the FPG enzyme should flip out the cytosine base paired with the scissile 8OG, not the target base itself.

Original languageEnglish (US)
Pages (from-to)93-108
Number of pages16
JournalMutation Research - DNA Repair
Volume487
Issue number3-4
DOIs
StatePublished - Dec 19 2001
Externally publishedYes

Fingerprint

DNA Repair
Repair
DNA
Substrates
Enzymes
B-Form DNA
DNA sequences
Cytosine
Molecular Dynamics Simulation
Static Electricity
Functional groups
Molecular dynamics
Cations
Electrostatics
Trajectories
8-hydroxyguanine
Computer simulation

Keywords

  • AMBER
  • Glycosylase
  • Nucleotide flipping
  • Oxidative DNA damage

ASJC Scopus subject areas

  • Toxicology
  • Genetics
  • Molecular Biology

Cite this

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title = "Backbone dynamics of DNA containing 8-oxoguanine: Importance for substrate recognition by base excision repair glycosylases",
abstract = "Except for the functional groups sited within the major or minor grooves, the bases of B-DNA are quite protected from the external environment. Enzymes that modify the bases often {"}flip out{"} the target into an extrahelical position before the chemistry step is carried out. Examples of this mechanism are the base excision repair glycosylases and the restriction enzyme methylases. The question arises about the mechanism of substrate recognition for these enzymes and how closely it is linked to the base flipping step. Molecular dynamics simulations (AMBER, PME electrostatics) of fully solvated, cation neutralized, DNA sequences containing 8-oxoguanine (8OG) and of appropriate normal (control) DNAs have been carried out. The dynamics trajectories were analyzed to identify those properties of the DNA structure in the vicinity of the altered base, or its dynamics, that could contribute to molecular discrimination between substrate and non-substrate DNA sites. The results predict that the FPG enzyme should flip out the cytosine base paired with the scissile 8OG, not the target base itself.",
keywords = "AMBER, Glycosylase, Nucleotide flipping, Oxidative DNA damage",
author = "Dodson, {M. L.} and Lloyd, {Robert (Stephen)}",
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TY - JOUR

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T2 - Importance for substrate recognition by base excision repair glycosylases

AU - Dodson, M. L.

AU - Lloyd, Robert (Stephen)

PY - 2001/12/19

Y1 - 2001/12/19

N2 - Except for the functional groups sited within the major or minor grooves, the bases of B-DNA are quite protected from the external environment. Enzymes that modify the bases often "flip out" the target into an extrahelical position before the chemistry step is carried out. Examples of this mechanism are the base excision repair glycosylases and the restriction enzyme methylases. The question arises about the mechanism of substrate recognition for these enzymes and how closely it is linked to the base flipping step. Molecular dynamics simulations (AMBER, PME electrostatics) of fully solvated, cation neutralized, DNA sequences containing 8-oxoguanine (8OG) and of appropriate normal (control) DNAs have been carried out. The dynamics trajectories were analyzed to identify those properties of the DNA structure in the vicinity of the altered base, or its dynamics, that could contribute to molecular discrimination between substrate and non-substrate DNA sites. The results predict that the FPG enzyme should flip out the cytosine base paired with the scissile 8OG, not the target base itself.

AB - Except for the functional groups sited within the major or minor grooves, the bases of B-DNA are quite protected from the external environment. Enzymes that modify the bases often "flip out" the target into an extrahelical position before the chemistry step is carried out. Examples of this mechanism are the base excision repair glycosylases and the restriction enzyme methylases. The question arises about the mechanism of substrate recognition for these enzymes and how closely it is linked to the base flipping step. Molecular dynamics simulations (AMBER, PME electrostatics) of fully solvated, cation neutralized, DNA sequences containing 8-oxoguanine (8OG) and of appropriate normal (control) DNAs have been carried out. The dynamics trajectories were analyzed to identify those properties of the DNA structure in the vicinity of the altered base, or its dynamics, that could contribute to molecular discrimination between substrate and non-substrate DNA sites. The results predict that the FPG enzyme should flip out the cytosine base paired with the scissile 8OG, not the target base itself.

KW - AMBER

KW - Glycosylase

KW - Nucleotide flipping

KW - Oxidative DNA damage

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