A Caltech Library Service

Long-range oxidative damage to cytosines in duplex DNA

Shao, Fangwei and O'Neill, Melanie A. and Barton, Jacqueline K. (2004) Long-range oxidative damage to cytosines in duplex DNA. Proceedings of the National Academy of Sciences of the United States of America, 101 (52). pp. 17914-17919. ISSN 0027-8424. PMCID PMC539793. doi:10.1073/pnas.0408128101.

PDF - Published Version
See Usage Policy.

[img] PDF (Supporting Figure 5) - Supplemental Material
See Usage Policy.

[img] PDF (Supporting Figure 6) - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


Charge transport (CT) through DNA has been found to occur over long molecular distances in a reaction that is sensitive to intervening structure. The process has been described mechanistically as involving diffusive charge-hopping among low-energy guanine sites. Using a kinetically fast electron hole trap, N-4-cyclopropylcytosine (C-CP), here we show that hole migration must involve also the higher-energy pyrimidine bases. In DNA assemblies containing either [Rh(phi)(2)(bpy')](3+) or an anthraquinone derivative, two high-energy photooxidants, appreciable oxidative damage at a distant C-CP is observed. The damage yield is modulated by lower-energy guanine sites on the same or complementary strand. Significantly, the efficiency in trapping at C-CP is equivalent to that at N-2-cyclopropylguanosine ((CP)G). Indeed, even when (CP)G and C-CP are incorporated as neighboring bases on the same strand, their efficiency of photodecomposition is comparable. Thus, CT is not simply a function of the relative energies of the isolated bases but instead may require orbital mixing among the bases. We propose that charge migration through DNA involves occupation of all of the DNA bases with radical delocalization within transient structure-dependent domains. These delocalized domains may form and break up transiently, facilitating and limiting CT. This dynamic delocalized model for DNA CT accounts for the sensitivity of the process to sequence-dependent DNA structure and provides a basis to reconcile and exploit DNA CT chemistry and physics.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Shao, Fangwei0000-0003-2007-3920
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2004 by the National Academy of Sciences. Contributed by Jacqueline K. Barton, November 3, 2004. We thank Dr. C. Dohno for technical help. This work was supported by National Institutes of Heath Grant GM49216. M.A.O. thanks the Natural Sciences and Engineering Research Council of Canada for a postdoctoral fellowship.
Funding AgencyGrant Number
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Subject Keywords:charge transport, delocalized domain, radical trap, base dynamics, mediated charge-transport, double-helical DNA, electron-transfer, hole-transport, hopping mechanism, adenine bases, guanine, dynamics, distance, repair
Issue or Number:52
PubMed Central ID:PMC539793
Record Number:CaltechAUTHORS:SHApnas04
Persistent URL:
Official Citation:Fangwei Shao, Melanie A. O'Neill, and Jacqueline K. Barton Long-range oxidative damage to cytosines in duplex DNA PNAS 2004 101 (52) 17914-17919; published ahead of print December 16, 2004, doi:10.1073/pnas.0408128101
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:971
Deposited By: Tony Diaz
Deposited On:17 Nov 2005
Last Modified:08 Nov 2021 19:06

Repository Staff Only: item control page