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            <title xml:lang="en">Radiation-induced formation of tandem lesions: mechanistic aspect</title>
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                <forename type="first">Jean-Luc</forename>
                <surname>Ravanat</surname>
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            <idno type="halRefHtml">&lt;i&gt;Workshop: “DNA damages: modeling and rationalize structure and reactivity”&lt;/i&gt;, Nov 2015, Lyon, France</idno>
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                <title xml:lang="en">Radiation-induced formation of tandem lesions: mechanistic aspect</title>
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                    <forename type="first">Jean-Luc</forename>
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              <p>During the last three decades considerable efforts have been made to determine the nature and  quantify  the  amount  of  lesions  produced  in  double  stranded  (ds)DNA  exposed  to  oxidative stress.  Nowadays,  an  almost  complete  decomposition  pathway  of  the  four  DNA  bases mediated by hydroxyl radicals and one electron-oxidation, the two damaging species of such a stress,  is  available.  About  70  different  DNA  lesions  have  been  identified  and  some  of  them have been quantified in cells exposed to ionizing radiations. Regarding the chemical aspects of formation of these lesions, most of the reactions identified at  the  nucleoside  level  were  also  found  to  occur  in  double  stranded  (ds)DNA.  However, differences exist and some modifications were found to be generated specifically in dsDNA. This highlights the fact that the 3D structure of DNA somehow plays an important role in the decomposition of the initially generated radicals. Attention  will  be  focused  during  the  presentation  on  the  formation  of  complex  DNA  lesions that  could  be  significantly  generated  through  a  single  oxidation  event.  Such  damages  are different to so-called locally multiple damage sites that are produced specifically by radiations as  a  consequence  of  multiple  ionization  processes.  These  include  tandem  DNA  lesions generated  through  peroxidation  reactions  and  also  intra-and  inter-strand  crosslinks.  These examples  indicate  that  the  described  mechanisms  of  decomposition  of  the  DNA  bases  could be  different  in  dsDNA  compared  to  that  observed  for  free  nucleosides. Moreover,  this  also indicates that in a cellular environment, biomolecules surrounding DNA could also play a role in the mechanisms of decomposition of initially produced DNA radicals. To  further  delineate  the  mechanisms  of  radiation-mediated  decomposition  of  DNA  bases  in dsDNA both experimental and theoretical approaches are required.</p>
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