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PhD position
DNA damage and repair induced by oxidation and reduction.
Mechanistic studies based on a joint electrochemical and photochemical approach.
The two principal mechanisms of charge transport through DNA are: 1) transfer of positive charges
(“holes”) and 2) transfer of negative charges (“excess electrons”). Both processes have biological importance.
Hole transfer is directly involved in the mechanism of DNA damage. Electron injection into DNA was found to
be a naturally occurring process for the repair of photodamages such as the thymine-thymine dimer by the
corresponding repair enzymes (“photolyases”).
Despite many work during the past 20 years, fundamental mechanistic issues related to DNA redox
properties remain to be elucidated, in particular those concerning the degree of coupling for electron and proton
transfer during base oxidation and reduction. This coupling could occur between base pairs but also between the
electroactive base and a surrounding proton acceptor (water or buffer molecule). The understanding of these
reactions is the first target of the project (see scheme). It is a key
step towards a better comprehension of both charge transport,
damage and repair processes in DNA. Another important issue
concerns electron transfer between amino acids and oxidized
DNA in proteins. These processes may lead either to repair or
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formation of DNA-protein cross-links products (damage). This
program will be also aim at deciphering the rate and mechanisms of such biologically relevant reactions, starting
from the study of simplified biomimetic molecules.
During the course of the PhD, electrochemical and time resolved photochemical studies of DNA bases
and oligonucleotides reduction and oxidation will be performed. Analysis of the results will benefit from the
recent design of a model for interpreting electrochemical proton-coupled electron transfers processes (see JACS
2007, 129, 9953 and references cited therein).
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This work is supported by the French national agency for research (ANR), the National Center for Scientific
Research (CNRS), the University Paris Diderot – Paris 7 and the European COST program ‘Free radicals in
chemical biology’ (CM0603). The student will be integrated into a team of seven people, including
electrochemists, photochemists and a synthetic chemist.
The candidate should be trained in molecular chemistry, and/or biophysics, and/or biochemistry. CV should be
sent to Prof. Marc Robert ([email protected]) and Prof. Jean-Michel Savéant ([email protected]). Salary : 1360 euros (net income). Starting date : no later than september 1 st 2008.
Web site of the laboratory : http://www.lemp7.cnrs.fr/index_en.htm