Impact of the oxidized guanine lesion spiroiminodihydantoin on the conformation and thermodynamic stability of a 15-mer DNA duplex

Fadzai Chinyengetere, Elizabeth R. Jamieson

Research output: Contribution to journalArticle

Abstract

Spiroiminodihydantoin (Sp) is a hyperoxidized guanine base produced from oxidation of the mutagenic DNA lesion 7,8-dihydro-8-oxo-2′-deoxguanosine (8-oxoG) by a variety of species including peroxynitrite, singlet oxygen, and the high-valent metals Ir(IV) and Cr(V). In this study, the conformation and thermodynamic stability of a 15-mer DNA duplex containing an Sp lesion are examined using spectroscopic techniques and differential scanning calorimetry (DSC). The Sp lesion does not alter the global B-form conformation of the DNA duplex as determined by circular dichroism spectroscopy. Thermal denaturation experiments find that Sp significantly lowers the thermal stability of the duplex by ∼20°C. The enthalpies, entropies, and free energies of duplex formation for 15-mers containing guanine, 8-oxoG, and Sp were determined by performing DSC experiments as well as van't Hoff analysis of UV melting spectroscopic data. The thermodynamic stability of the Sp duplex is significantly reduced compared to that of both the 8-oxoG and parent G duplexes, with the thermodynamic destabilization being enthalpic in origin. The thermodynamic impact of the Sp lesion is compared to what is found for other types of DNA base damage and discussed in relation to how the presence of this lesion could affect cellular processes, in particular the recognition and repair of these adducts by the base excision repair enzymes.

Original languageEnglish (US)
Pages (from-to)2584-2591
Number of pages8
JournalBiochemistry
Volume47
Issue number8
DOIs
StatePublished - Feb 26 2008
Externally publishedYes

Fingerprint

Guanine
Thermodynamics
Conformations
Thermodynamic stability
DNA
Differential Scanning Calorimetry
Differential scanning calorimetry
Repair
Hot Temperature
B-Form DNA
Circular dichroism spectroscopy
Singlet Oxygen
Denaturation
Peroxynitrous Acid
Entropy
Circular Dichroism
spiroiminodihydantoin
DNA Repair
Freezing
Free energy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Impact of the oxidized guanine lesion spiroiminodihydantoin on the conformation and thermodynamic stability of a 15-mer DNA duplex. / Chinyengetere, Fadzai; Jamieson, Elizabeth R.

In: Biochemistry, Vol. 47, No. 8, 26.02.2008, p. 2584-2591.

Research output: Contribution to journalArticle

@article{cc75230059234a00b72ec8a83856f841,
title = "Impact of the oxidized guanine lesion spiroiminodihydantoin on the conformation and thermodynamic stability of a 15-mer DNA duplex",
abstract = "Spiroiminodihydantoin (Sp) is a hyperoxidized guanine base produced from oxidation of the mutagenic DNA lesion 7,8-dihydro-8-oxo-2′-deoxguanosine (8-oxoG) by a variety of species including peroxynitrite, singlet oxygen, and the high-valent metals Ir(IV) and Cr(V). In this study, the conformation and thermodynamic stability of a 15-mer DNA duplex containing an Sp lesion are examined using spectroscopic techniques and differential scanning calorimetry (DSC). The Sp lesion does not alter the global B-form conformation of the DNA duplex as determined by circular dichroism spectroscopy. Thermal denaturation experiments find that Sp significantly lowers the thermal stability of the duplex by ∼20°C. The enthalpies, entropies, and free energies of duplex formation for 15-mers containing guanine, 8-oxoG, and Sp were determined by performing DSC experiments as well as van't Hoff analysis of UV melting spectroscopic data. The thermodynamic stability of the Sp duplex is significantly reduced compared to that of both the 8-oxoG and parent G duplexes, with the thermodynamic destabilization being enthalpic in origin. The thermodynamic impact of the Sp lesion is compared to what is found for other types of DNA base damage and discussed in relation to how the presence of this lesion could affect cellular processes, in particular the recognition and repair of these adducts by the base excision repair enzymes.",
author = "Fadzai Chinyengetere and Jamieson, {Elizabeth R.}",
year = "2008",
month = "2",
day = "26",
doi = "10.1021/bi701502t",
language = "English (US)",
volume = "47",
pages = "2584--2591",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Impact of the oxidized guanine lesion spiroiminodihydantoin on the conformation and thermodynamic stability of a 15-mer DNA duplex

AU - Chinyengetere, Fadzai

AU - Jamieson, Elizabeth R.

PY - 2008/2/26

Y1 - 2008/2/26

N2 - Spiroiminodihydantoin (Sp) is a hyperoxidized guanine base produced from oxidation of the mutagenic DNA lesion 7,8-dihydro-8-oxo-2′-deoxguanosine (8-oxoG) by a variety of species including peroxynitrite, singlet oxygen, and the high-valent metals Ir(IV) and Cr(V). In this study, the conformation and thermodynamic stability of a 15-mer DNA duplex containing an Sp lesion are examined using spectroscopic techniques and differential scanning calorimetry (DSC). The Sp lesion does not alter the global B-form conformation of the DNA duplex as determined by circular dichroism spectroscopy. Thermal denaturation experiments find that Sp significantly lowers the thermal stability of the duplex by ∼20°C. The enthalpies, entropies, and free energies of duplex formation for 15-mers containing guanine, 8-oxoG, and Sp were determined by performing DSC experiments as well as van't Hoff analysis of UV melting spectroscopic data. The thermodynamic stability of the Sp duplex is significantly reduced compared to that of both the 8-oxoG and parent G duplexes, with the thermodynamic destabilization being enthalpic in origin. The thermodynamic impact of the Sp lesion is compared to what is found for other types of DNA base damage and discussed in relation to how the presence of this lesion could affect cellular processes, in particular the recognition and repair of these adducts by the base excision repair enzymes.

AB - Spiroiminodihydantoin (Sp) is a hyperoxidized guanine base produced from oxidation of the mutagenic DNA lesion 7,8-dihydro-8-oxo-2′-deoxguanosine (8-oxoG) by a variety of species including peroxynitrite, singlet oxygen, and the high-valent metals Ir(IV) and Cr(V). In this study, the conformation and thermodynamic stability of a 15-mer DNA duplex containing an Sp lesion are examined using spectroscopic techniques and differential scanning calorimetry (DSC). The Sp lesion does not alter the global B-form conformation of the DNA duplex as determined by circular dichroism spectroscopy. Thermal denaturation experiments find that Sp significantly lowers the thermal stability of the duplex by ∼20°C. The enthalpies, entropies, and free energies of duplex formation for 15-mers containing guanine, 8-oxoG, and Sp were determined by performing DSC experiments as well as van't Hoff analysis of UV melting spectroscopic data. The thermodynamic stability of the Sp duplex is significantly reduced compared to that of both the 8-oxoG and parent G duplexes, with the thermodynamic destabilization being enthalpic in origin. The thermodynamic impact of the Sp lesion is compared to what is found for other types of DNA base damage and discussed in relation to how the presence of this lesion could affect cellular processes, in particular the recognition and repair of these adducts by the base excision repair enzymes.

UR - http://www.scopus.com/inward/record.url?scp=39749192567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39749192567&partnerID=8YFLogxK

U2 - 10.1021/bi701502t

DO - 10.1021/bi701502t

M3 - Article

C2 - 18281959

AN - SCOPUS:39749192567

VL - 47

SP - 2584

EP - 2591

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 8

ER -