Electron trap for DNA-bound repair enzymes: a strategy for DNA-mediated signaling

Proceedings of the National Academy of Sciences of the United States of America
Eylon YavinJacqueline K Barton

Abstract

Despite a low copy number within the cell, base excision repair (BER) enzymes readily detect DNA base lesions and mismatches. These enzymes also contain [Fe4S4] clusters, yet a redox role for these iron cofactors had been unclear. Here, we provide evidence that BER proteins may use DNA-mediated redox chemistry as part of a signaling mechanism to detect base lesions. By using chemically modified bases, we show electron trapping on DNA in solution with bound BER enzymes by electron paramagnetic resonance (EPR) spectroscopy. We demonstrate electron transfer from two BER proteins, Endonuclease III (EndoIII) and MutY, to modified bases in DNA containing oxidized nitroxyl radical EPR probes. Electron trapping requires that the modified base is coupled to the DNA pi-stack, and trapping efficiency is increased when a noncleavable MutY substrate analogue is located distally to the trap. These results are consistent with DNA binding leading to the activation of the repair proteins toward oxidation. Significantly, these results support a mechanism for DNA repair that involves DNA-mediated charge transport.

References

May 16, 1989·Biochemistry·R P CunninghamM H Emptage
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T R O'Connor, J Laval
Jan 1, 1994·Annual Review of Biochemistry·B Demple, L Harrison
Aug 22, 1996·Nature·D B HallJ K Barton
May 1, 1997·Chemistry & Biology·G L Verdine, S D Bruner
Feb 18, 1999·Chemistry & Biology·M E NúñezJ K Barton
Apr 15, 2000·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·H Beinert
Oct 4, 2000·Nature Biotechnology·E M BoonJ K Barton
Sep 6, 2001·Journal of the American Chemical Society·P K Bhattacharya, J K Barton
Mar 5, 2002·Nature Biotechnology·Elizabeth M BoonJacqueline K Barton
Jan 22, 2003·Biochemistry·Anthony W Francis, Sheila S David
Jul 4, 2003·The EMBO Journal·J Christopher Fromme, Gregory L Verdine
Feb 5, 2004·Journal of the American Chemical Society·Sascha BreegerThomas Carell
Nov 26, 2004·Journal of the American Chemical Society·Takeo Ito, Steven E Rokita
Mar 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eylon YavinJacqueline K Barton
Mar 17, 2005·Bioconjugate Chemistry·Amie K Boal, Jacqueline K Barton
Apr 7, 2005·Current Opinion in Chemical Biology·Olga A Lukianova, Sheila S David
Jun 9, 2005·Biochemistry·Amie K BoalJacqueline K Barton
Mar 2, 1998·Angewandte Chemie·Eric MeggersBernd Giese

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Citations

Mar 11, 2010·Chemical Reviews·Joseph C Genereux, Jacqueline K Barton
Jan 9, 2009·Journal of the American Chemical Society·Tal Z MarkusCynthia J Burrows
Jan 6, 2010·Journal of the American Chemical Society·Joseph C GenereuxJacqueline K Barton
Sep 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Amie K BoalJacqueline K Barton
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Pamela A SontzJacqueline K Barton
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Cynthia J Burrows, Aaron M Fleming
Nov 28, 2015·The FEBS Journal·Carlos H Trasviña-ArenasLuis G Brieba
Mar 5, 2016·Cell Chemical Biology·Anna R ArnoldJacqueline K Barton
Mar 17, 2015·Mutation Research·Ana Helena Sales de OliveiraLucymara Fassarella Agnez-Lima
Aug 8, 2009·FEMS Microbiology Reviews·Bjørn DalhusMagnar Bjørås
Mar 4, 2008·Current Opinion in Chemical Biology·Edward J MerinoJacqueline K Barton
Feb 23, 2012·Scientific Reports·Chi-Tin ShihRudolf A Römer
Mar 28, 2013·Angewandte Chemie·Yaming YuGilbert Nöll
Oct 2, 2009·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Ye-Fei WangCheng-Bu Liu
Feb 26, 2009·The Journal of Physical Chemistry. a·Raanan CarmieliMichael R Wasielewski
Sep 8, 2009·The Journal of Physical Chemistry. a·Ye-Fei WangCheng-Bu Liu
Jun 30, 2007·Journal of Inorganic Biochemistry·Amie K BoalJacqueline K Barton
Jan 19, 2007·The Journal of Physical Chemistry. B·Donato M CeresJacqueline K Barton
Sep 14, 2006·Journal of the American Chemical Society·Alon A GorodetskyJacqueline K Barton
Dec 7, 2007·The Journal of Physical Chemistry. B·I-Chun LinUrsula Rothlisberger
Jun 20, 2008·Chemical Reviews·Fabien Boussicault, Marc Robert

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