Redox signaling between DNA repair proteins for efficient lesion detection

被引:103
作者
Boal, Amie K. [4 ]
Genereux, Joseph C. [4 ]
Sontz, Pamela A. [4 ]
Gralnick, Jeffrey A. [5 ]
Newman, Dianne K. [1 ,2 ,3 ]
Barton, Jacqueline K. [4 ]
机构
[1] MIT, Dept Biol & Earth, Cambridge, MA 02139 USA
[2] MIT, Dept Atomospher & Planetary Sci, Cambridge, MA 02139 USA
[3] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
[4] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA
[5] Univ Minnesota, Inst Biotechnol, Dept Microbiol, St Paul, MN 55108 USA
基金
美国国家卫生研究院;
关键词
DNA charge transport; DNA damage; iron-sulfur proteins; oxidative stress; MEDIATED CHARGE-TRANSPORT; ENZYME ENDONUCLEASE-III; BASE-EXCISION-REPAIR; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; OXIDATIVE DAMAGE; IN-VIVO; MUTY; 8-OXOGUANINE; GLYCOSYLASE;
D O I
10.1073/pnas.0908059106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Base excision repair (BER) enzymes maintain the integrity of the genome, and in humans, BER mutations are associated with cancer. Given the remarkable sensitivity of DNA-mediated charge transport (CT) to mismatched and damaged base pairs, we have proposed that DNA repair glycosylases (EndoIII and MutY) containing a redox-active [4Fe4S] cluster could use DNA CT in signaling one another to search cooperatively for damage in the genome. Here, we examine this model, where we estimate that electron transfers over a few hundred base pairs are sufficient for rapid interrogation of the full genome. Using atomic force microscopy, we found a redistribution of repair proteins onto DNA strands containing a single base mismatch, consistent with our model for CT scanning. We also demonstrated in Escherichia coli a cooperativity between EndoIII and MutY that is predicted by the CT scanning model. This relationship does not require the enzymatic activity of the glycosylase. Y82A EndoIII, a mutation that renders the protein deficient in DNA-mediated CT, however, inhibits cooperativity between MutY and EndoIII. These results illustrate how repair proteins might efficiently locate DNA lesions and point to a biological role for DNA-mediated CT within the cell.
引用
收藏
页码:15237 / 15242
页数:6
相关论文
共 43 条
[1]   A role for DNA-mediated charge transport in regulating p53: Oxidation of the DNA-bound protein from a distance [J].
Augustyn, Katherine E. ;
Merino, Edward J. ;
Barton, Jacqueline K. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (48) :18907-18912
[2]   DIFFUSION-DRIVEN MECHANISMS OF PROTEIN TRANSLOCATION ON NUCLEIC-ACIDS .1. MODELS AND THEORY [J].
BERG, OG ;
WINTER, RB ;
VONHIPPEL, PH .
BIOCHEMISTRY, 1981, 20 (24) :6929-6948
[3]   Electrochemical detection of lesions in DNA [J].
Boal, AK ;
Barton, JK .
BIOCONJUGATE CHEMISTRY, 2005, 16 (02) :312-321
[4]   DNA-bound redox activity of DNA repair glycosylases containing [4Fe-4S] clusters [J].
Boal, AK ;
Yavin, E ;
Lukianova, OA ;
O'Shea, VL ;
David, SS ;
Barton, JK .
BIOCHEMISTRY, 2005, 44 (23) :8397-8407
[5]   Mutation detection by electrocatalysis at DNA-modified electrodes [J].
Boon, EM ;
Ceres, DM ;
Drummond, TG ;
Hill, MG ;
Barton, JK .
NATURE BIOTECHNOLOGY, 2000, 18 (10) :1096-1100
[6]   DNA-mediated charge transport for DNA repair [J].
Boon, EM ;
Livingston, AL ;
Chmiel, NH ;
David, SS ;
Barton, JK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) :12543-12547
[7]   An electrical probe of protein-DNA interactions on DNA-modified surfaces [J].
Boon, EM ;
Salas, JE ;
Barton, JK .
NATURE BIOTECHNOLOGY, 2002, 20 (03) :282-286
[8]   Oxidative nucleobase modifications leading to strand scission [J].
Burrows, CJ ;
Muller, JG .
CHEMICAL REVIEWS, 1998, 98 (03) :1109-1151
[9]   MUTYH-associated polyposis- : From defect in base excision repair to clinical genetic testing [J].
Cheadle, Jeremy P. ;
Sampson, Julian. R. .
DNA REPAIR, 2007, 6 (03) :274-279
[10]   Direct visualization of a DNA glycosylase searching for damage [J].
Chen, LW ;
Haushalter, KA ;
Lieber, CM ;
Verdine, GL .
CHEMISTRY & BIOLOGY, 2002, 9 (03) :345-350