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Oxidation by DNA charge transport damages conserved sequence block II, a regulatory element in mitochondrial DNA.
Biochemistry. 2007 Mar 13; 46(10):2805-11.B

Abstract

Sites of oxidative damage in mitochondrial DNA have been identified on the basis of DNA-mediated charge transport. Our goal is to understand which sites in mitochondrial DNA are prone to oxidation at long range and whether such oxidative damage correlates with cancerous transformation. Here we show that a primer extension reaction can be used to monitor directly oxidative damage to authentic mitochondrial DNA through photoreactions with a rhodium intercalator. The complex [Rh(phi)2bpy]Cl3 (phi = 9,10-phenanthrenequinone diimine) binds to DNA without sequence specificity and, upon photoactivation, either promotes strand breaks directly at the binding site or promotes one-electron oxidative damage; comparing the sites of base oxidation to direct strand breaks reveals the oxidative damage that arises from a distance through DNA-mediated charge transport. Significantly, base oxidation by charge transport overlaps with known mutational hot spots associated with cancers at nucleotides surrounding positions 263 and 303; the latter is known as conserved sequence block II and is vital to DNA replication. Since DNA base oxidation at conserved sequence block II should weaken the ability of damaged mitochondrial genomes to be replicated, DNA-mediated charge transport may provide a protection mechanism for excluding damaged DNA.

Authors+Show Affiliations

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17302436

Citation

Merino, Edward J., and Jacqueline K. Barton. "Oxidation By DNA Charge Transport Damages Conserved Sequence Block II, a Regulatory Element in Mitochondrial DNA." Biochemistry, vol. 46, no. 10, 2007, pp. 2805-11.
Merino EJ, Barton JK. Oxidation by DNA charge transport damages conserved sequence block II, a regulatory element in mitochondrial DNA. Biochemistry. 2007;46(10):2805-11.
Merino, E. J., & Barton, J. K. (2007). Oxidation by DNA charge transport damages conserved sequence block II, a regulatory element in mitochondrial DNA. Biochemistry, 46(10), 2805-11.
Merino EJ, Barton JK. Oxidation By DNA Charge Transport Damages Conserved Sequence Block II, a Regulatory Element in Mitochondrial DNA. Biochemistry. 2007 Mar 13;46(10):2805-11. PubMed PMID: 17302436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidation by DNA charge transport damages conserved sequence block II, a regulatory element in mitochondrial DNA. AU - Merino,Edward J, AU - Barton,Jacqueline K, Y1 - 2007/02/16/ PY - 2007/2/17/pubmed PY - 2007/5/16/medline PY - 2007/2/17/entrez SP - 2805 EP - 11 JF - Biochemistry JO - Biochemistry VL - 46 IS - 10 N2 - Sites of oxidative damage in mitochondrial DNA have been identified on the basis of DNA-mediated charge transport. Our goal is to understand which sites in mitochondrial DNA are prone to oxidation at long range and whether such oxidative damage correlates with cancerous transformation. Here we show that a primer extension reaction can be used to monitor directly oxidative damage to authentic mitochondrial DNA through photoreactions with a rhodium intercalator. The complex [Rh(phi)2bpy]Cl3 (phi = 9,10-phenanthrenequinone diimine) binds to DNA without sequence specificity and, upon photoactivation, either promotes strand breaks directly at the binding site or promotes one-electron oxidative damage; comparing the sites of base oxidation to direct strand breaks reveals the oxidative damage that arises from a distance through DNA-mediated charge transport. Significantly, base oxidation by charge transport overlaps with known mutational hot spots associated with cancers at nucleotides surrounding positions 263 and 303; the latter is known as conserved sequence block II and is vital to DNA replication. Since DNA base oxidation at conserved sequence block II should weaken the ability of damaged mitochondrial genomes to be replicated, DNA-mediated charge transport may provide a protection mechanism for excluding damaged DNA. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/17302436/Oxidation_by_DNA_charge_transport_damages_conserved_sequence_block_II_a_regulatory_element_in_mitochondrial_DNA_ L2 - https://dx.doi.org/10.1021/bi062024+ DB - PRIME DP - Unbound Medicine ER -