Direct observation of radical intermediates in protein-dependent DNA charge transport

被引:88
作者
Wagenknecht, HA [1 ]
Rajski, SR [1 ]
Pascaly, M [1 ]
Stemp, EDA [1 ]
Barton, JK [1 ]
机构
[1] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA
关键词
D O I
10.1021/ja003986l
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Charge migration through the DNA base stack has been probed both spectroscopically, to observe the formation of radical intermediates, and biochemically, to assess irreversible oxidative DNA damage. Charge transport and radical trapping were examined in DNA assemblies in the presence of a site-specifically bound methyltransferase HhaI mutant and an intercalating ruthenium photooxidant using the flash-quench technique. The methyltransferase mutant, which can flip out a base and insert a tryptophan side chain within the DNA cavity, is found to activate long-range hole transfer through the base pair stack. Protein-dependent DNA charge transport is observed over 50 Angstrom with guanine radicals formed > 10(6) s(-1): hole transport through DNA over this distance is not rate-limiting. Given the time scale and distance regime, such protein-dependent DNA charge transport chemistry requires consideration physiologically.
引用
收藏
页码:4400 / 4407
页数:8
相关论文
共 49 条
[31]   Robust charge transport in DNA double crossover assemblies [J].
Odom, DT ;
Dill, EA ;
Barton, JK .
CHEMISTRY & BIOLOGY, 2000, 7 (07) :475-481
[32]   Enzymatic C5-cytosine methylation of DNA: Mechanistic implications of new crystal structures for HhaI methyltransferase-DNA-AdoHcy complexes [J].
OGara, M ;
Klimasauskas, S ;
Roberts, RJ ;
Cheng, XD .
JOURNAL OF MOLECULAR BIOLOGY, 1996, 261 (05) :634-645
[33]   First observation of the key intermediate in the ''light-switch'' mechanism of [Ru(phen)(2)dppz](2+) [J].
Olson, EJC ;
Hu, D ;
Hormann, A ;
Jonkman, AM ;
Arkin, MR ;
Stemp, EDA ;
Barton, JK ;
Barbara, PF .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (47) :11458-11467
[34]   Effect of guanine stacking on the oxidation of 8-oxoguanine in B-DNA [J].
Prat, F ;
Houk, KN ;
Foote, CS .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (04) :845-846
[35]   DNA-mediated electron transfer [J].
Priyadarshy, S ;
Risser, SM ;
Beratan, DN .
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, 1998, 3 (02) :196-200
[36]   CHARGE-TRANSFER IN PEPTIDES - PULSE-RADIOLYSIS INVESTIGATION OF ONE-ELECTRON REACTIONS IN DIPEPTIDES OF TRYPTOPHAN AND TYROSINE [J].
PRUTZ, WA ;
LAND, EJ .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1979, 36 (05) :513-520
[37]   Protein-modulated DNA electron transfer [J].
Rajski, SR ;
Kumar, S ;
Roberts, RJ ;
Barton, JK .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (23) :5615-5616
[38]   DNA repair: models for damage and mismatch recognition [J].
Rajski, SR ;
Jackson, BA ;
Barton, JK .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2000, 447 (01) :49-72
[39]   Base flipping [J].
Roberts, RJ ;
Cheng, XD .
ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :181-+
[40]   Mapping of the hot spots for DNA damage by one-electron oxidation: Efficacy of GG doublets and GGG triplets as a trap in long-range hole migration [J].
Saito, I ;
Nakamura, T ;
Nakatani, K ;
Yoshioka, Y ;
Yamaguchi, K ;
Sugiyama, H .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (48) :12686-12687