Oral

·    Clustered DNA damage, mutations and radiation quality, P. O'Neill (Invited Lecture), C. Pearson & M. Lomax, Ionising Radiation Quality, Molecular Mechanisms, Cellular Effects, and Their Consequences for Low Level Risk Assessment and Radiation Therapy, 14th Symposium on Microdosimetry, Venice, Italy, 13-18 November, 2005

·    The mutability of clustered DNA damage in BER deficient E. coli. C.. Pearson, N. Shikazono, J. Thacker, P. O'Neill, European Society for Radiation Research /ARR meeting Leicester, UK 5-8 September 2005

·    Effect of NAD⁺ on the repair of simple or clustered DNA damaged sites, Sophie Bellon, Keystone Symposia Genome Instability and Repair Taos, USA 15-21 March 2005. (Sophie Bellon Scholarship winner)

·    Application of UV laser photochemistry to the studies of histone-DNA interactions and transcription factor binding to nucleosomes. D. Angelov, H. Menoni, J. Cadet, P. Bouvet, S. Dimitrov. 11th Congress of the European Society for Photobiology September 3 - 8, 2005, Aix-les-Bains – France

·    Independent Synthesis of Modified Nucleosides, Products of Guanine Oxidation , A. Salgado, D. Panagopoulos, T. Gimisis. XIII Symposium on the Chemistry of Nucleic Acid Components, 3-9 September 2005, Spindlevur, Mlyn, Czech Republic..

·    Estereoselectividad durante la fotosensibilización de la timidina y de la 2´- desoxiguanosina por el ketoprofeno. V. Lhiaubet-Vallet, S. Encinas, M. A. Miranda, VII Congreso de Fotoquímica de la Real Sociedad Española de Fotoquímica.Logroño. España. 22-24 June 2005.

·    Estereoselectividad en procesos fotoquímicos de interés biológico. M. A. Miranda (Plenary lecture) VII Congreso de Fotoquímica de la Real Sociedad Española de Fotoquímica.Logroño. España. 22-24 June 2005.

• Drug-nucleoside interactions in the excited states: A model to investigate the basic mechanisms of drug-photosensitized DNA damage. M. A. Miranda (Invited Lecture), XI Congress of the European Society for Photobiology, Aix –les-Bains. 3-8 September, 2005.

Posters

·    Clustered DNA damage: 5,6-dihydrothymine retards base excision repair of an abasic site by xrs5 nuclear extracts S. Byrne, M. Lomax & P. O'Neill, Responses to DNA Damage: Insights from Chemical, Biochemical, Structural Biology and Cellular Studies Brighton , UK 19-21 September 2005

·    An in vivo investigation into the mutability of clustered DNA damage in base excision repair deficient E. coli., C. G. Pearson, N. Shikazono, J. Thacker and P. O'Neill, Keystone meeting

·    An in vivo investigation into the mutability of clustered DNA damage in base excision repair deficient E. coli. C. Pearson, N. Shikazono, J. Thacker and P. O'Neill, 9^th International Wolfsberg Meeting 2005 Ermatingen, Switzerland, 18-20 June, 2005

·    Effect of NAD⁺ on the repair of simple or clustered DNA damaged sites, Sophie Bellon, Martine Lomax, Peter O'Neill, Keystone Symposia Genome Instability and Repair Taos, USA 15-21 march 2005.

·    DNA-DNA crosslinking at guanines: a new and major class of oxidatively generated damage by UV laser biphotonic ionization in DNA. H. Menoni, D. Gasparutto, J.-L. Ravanat, J. Cadet, S. Dimitrov, D. Angelov. 11th Congress of the European Society for Photobiology September 3 - 8, 2005, Aix-les-Bains – France

·    β-D-Glucopyranosyl Nucleosides as Potential Inhibitors of Glucogen Phosphorylase Crina Cismas. 13^th European Carbohydrate Symposium, August 21-26, 2005, Bratislava, Slovakia .

·    Estudio Fotoquímico y de Radiólisis Pulsada de la 8-Bromo-2´- Desoxi-Inosina. L. Jiménez, S. Encinas, M, A. Miranda, M. Russo, M. D´Angelantonio, Q. G. Mulazzani, C. Chatgilialoglu, VII Congreso de Fotoquímica de la Real Sociedad Española de Fotoquímica.Logroño. España. 22-24 June 2005.

·    Estudios Fotofísicos y Fotoquímicos de Derivados Nucleosídicos Precursores de Daño Radicalario al ADN. C. Paris, S. Encinas, T. Gimisis, M. A. Miranda, C. Paris, S. Encinas, T. Gimisis, M. A. Miranda, VII Congreso de Fotoquímica de la Real Sociedad Española de Fotoquímica.Logroño. España. 22-24 June 2005.

·    Steady-state and time-resolved studies on Ketoprofen-Thymine dyads. C. Paris, N. Belmadoui, M. J. Climent, S. Encinas, M. A. Miranda, XI Congress of the European Society for Photobiology, Aix –les-Bains. 3-8 September, 2005.

·    Study of 8-bromo-2´-deoxyinosine by photochemical and radiolytic methods. L. Jiménez, S. Encinas, M, A. Miranda, M. Russo, M. D´Angelantonio, Q. G. Mulazzani, C. Chatgilialoglu, XI Congress of the European Society for Photobiology, Aix –les-Bains. 3-8 September, 2005.

Network oral presentations

2^nd EU-Network meeting CLUSTOXDNA, Munich, 23-26 February 2005

·            Selective generation and reactivity of 2'-deoxyinosin-5'-yl radical, Liliana B. Jimenez (Partner 5)

·            Time-resolved experiments on 5'-pivaloyl substituted (deoxy)guanosine derivatives, Cecilia G. Paris (Partner 5, ESR)

·            The reaction of hydrated electrons with 8-bromoguanine derivatives, Clara Caminal (Partner 4, ESR)

·            Oxidatively generated damage to DNA new insights into the formation of clustered damage, Jean Cadet (Partner 2)

·            Oligonucleotides containing (5'S) and (5'R) 8,5'-cyclo2'-deoxyadenosine. Synthesis, characterization by nuclear magnetic resonance, thermodynamic and biological properties, Boleslaw Karwowski (Partner 2, ER)

·            Independent photochemical generation of guanosine base radicals, Thanasis Gimisis (Partner 6)

·            Independent synthesis of parabanic acid nucleosides, Antonio Salgado Serrano (Partner 6, ER)

·            DNA repair of oxidative and UV-induced DNA lesions on an atomic level, Thomas Carell (Partner 3)

·            Excess electron Transfer into DNA: 8-BrAdo as electron acceptor, Antonio Manetto (Partner 3, ESR)

·            Synthesis of a carbocycle anologue of the 5-hydroxy-5-methylhydantoin, incorporation into oligonucleotides and comparison with that containing the natural DNA lesion, Maria Izquierdo (Partner 3)

·            Chromatin goes global, Dimitar Angelov (Partner 7)

·            Repair of clustered lesions within positioned mono and di-nucleosomes, Herve Menoni (Partner 7, ESR)

·            Consequences of clustered oxidative DNA modifications in cells, Bernd Epe

·            Effect if NAD+ in base excision repair of simple or clustered DNA damaged site, Sophie Bellon (Partner 1, ER)

·            Clustered DNA damage: 5,6-dihydrothymine retards base excision repair of an abasic site by XRSS nuclear extracts, Shaun Byrne (Partner 1)

3^nd European network meeting CLUSTOXDNA, Athens, 29 Sept – 2 Oct 2005

·            Independent synthesis of modified nucleosides, products of guanine oxidation, Antonio Salgado (Partner 6, ER)

·            A new approach for the incorporation of the FaPy.dA lesion into oligonucleotides, Simone Arnold (Partner 3)

·            Synthesis of a carbocycle analogue of the 5-hydroxy-5-methylhydantoin, incorporation into oligonucleotides and comparison with the natural DNA lesion, Maria Izquierdo (Partner 3)

·            Effect of (5'S)-5',8-cyclo-2'deoxyadenosine on the conformation of di and trinucleotides. Influence of cdA on base-excision repair system. Experimental and theoretical approaches, Boleslaw Karwowski (Partner 2, ER)

·            An insight into the stereoselectivity of the C5'-adenosyl radical cyclization onto the purine moiety, Maria Luisa Navacchia (Partner 4)

·            Chemical Radiation Studies of 8-Bromo-2'-deoxyinosine and 8-bromoinosine in aqueous solutions, Maria Luisa Russo (Partner 4)

·            Structural and chemical properties of 2'-deoxyadenosin-1'-yl radical, V. Tamara Perchyonok (Partner 4, ER)

·            Excess electron transfer through DNA investigated with differently strong electron acceptors reveals complex sequence dependence, Antonio Manetto (Partner 3, ESR)

·            Photochemical studies and time resolved experiments on synthetic nucleoside derivatives and ketoprofen thymine dyads, Cecilia Paris (Partner 5, ESR)

·            Cycloreversion of pyrimidine oxetanes through single electron transfer from excited carprofen derivatives, Jerome Trzcionka (Partner 5, ER)

·            DNA-DNA crosslinking at guanines: a new and major class of oxidatively generated damage by UV laser biphotonic ionization in DNA, Herve Menoni (Partner 7, ESR)

·            Repair kinetics of clustered oxidative DNA lesions in mammalian cells, Andrij Khobta (Partner 8, ER)

·            Thymine glycol within clustered DNA damage: influence in damage excision by glycosylases, and the base excision repair of an abasic site or a single strand break by XRS5 nuclear extracts, Sophie Bellon (Partner 1, ER)

1)          S. Bellon (ER MRC RAGSU), attended the annual scientific meeting of the Genome Stability Network,7th January 2005 in Cambridge, UK.

2)          S. Bellon (ER MRC RAGSU), attended the annual scientific meeting of the Genome Stability Network,7th January 2006 in Cambridge, UK.

3)          C. G. Paris (ESR, NKUA) participated in II Mediterranean Meeting on Organic Chemistry (Almeria, December 2004).

4)          Attendance at Network meetings

All the recruited ESR and ER have orally presenting their research and several have chaired the sessions at the Network Workshop organised in Munich and Athens. The list of talks is included in appendix

MRC RAGSU (ER - Sophie Bellon)

· Training others on-the-job, 10 May 2005 at MRC Harwell

· January 2005. Involvement in organisation of Oxfordshire Science week for Group of schoolchildren involving a hands-on demonstration of DNA footprinting.

CEA (Boleslaw Karwowski, ER)

· undertaking a training course (2 h per week) for beginners in French.

LMU MUENCHEN (ESRs)

· actively participated in weekly group seminars.

CEA.ISOF

UPVLC (G. Paris, ESR)

spent two weeks attending an intensive teaching period involving 40 PhD students from 6 Spanish Universities. She has receiving specific training on presentation skills and presented her preliminary results ‘in house'.

NKUA (Antonio Salgado, ER)

attended the “XIII Symposium on the Chemistry of Nucleic Acid Components” that took place in Spindlevur, Mlyn, Czech Republic, between the 3^rd and 9^th of September, 2005. He gave an oral presentation entitled “Independent Synthesis of Modified Nucleosides, Products of Guanine Oxidation”.

Dr Crina Cismas (ER)

attended the “13^th European Carbohydrate Symposium” that took place in Bratislava, Slovakia between August 21-26, 2005. She gave a poster presentation entitled “β-D-Glucopyranosyl Nucleosides as Potential Inhibitors of Glucogen Phosphorylase”.

ISSP-BAS (Hervé Menoni, ESR)

2 presentations at laboratory meetings. He has received training in tissue culture techniques and undertaken an animal handling course.

UNIMAINZ (Andriy Khobta, ER)

actively participated in the weekly group seminars and presented data on three international meetings with collaborating groups in Mainz, Paris and Oslo

MRC RAGSU (ER - Sophie Bellon)

Inviting by the CEA PhD student association (AITAP) to talk about the post doctoral experience abroad 30 June 2005

List of publications arising in part from the research of the Groups in support of the Research Achievements.

1.          M. Ober, U. Linne, J. Gierlich, T. Carell,. The two main oxydative DNA lesions 8-oxo-7,8-dihydroguanine and 2,6-diamino-5-formamido-4-hydroxypyrimidine exhibit strongly different pairing characteristics. Angew. Chem. Int. Ed. 42, 4947-4951 (2003).

2.          J. Rivière, F. Bergeron, S. Tremblay, D. Gasparutto, J. Cadet and J.R. Wagner, J. Am. Chem. Soc., 126, 6548-6549 (2004).

3.          F. Coste, M. Ober, T. Carell, S. Boiteux, C. Zelwer, B. Castaing, J. Biol. Chem. 279, 44074-44083 (2004).

4.          P. Regulus, S. Spessotto, M. Gateau , J. Cadet, A. Favier & J.-L. Ravanat, J. Rapid Mass Spectrom., 18, 2223-2228 (2004).

5.          De Champdoré, M.; De Napoli, L.; Montesarchio, D.; Piccialli, G.; Caminal C.; Mulazzani, Q. G.; Navacchia, M. L.; Chatgilialoglu, C. Chem. Commun. 1756–1757 (2004).

6.          L. M. Kundu, U. Linne, M. Marahiel, T. Carell, Chem. Eur. J. 10, 5697-5705 (2004)

7.          D. Angelov et al, Mol. Cell, 2003. 1033-1041; EMBO J. 23, 3815-3824 (2004).

8.          Lomax, M.. E., Cunniffe, S. and O'Neill, P. 8-OxoG retards the activity of the ligase III/XRCC1 complex during the repair of a single-strand break, when present within a clustered DNA damage site.DNA Repair, 3, 289-299 (2004).

9.          Pearson, C. G., Shikazono, N., Thacker, J. and O'Neill, P. Enhanced mutagenic potential of 8-oxo-7,8-dihydroguanine when present within a clustered DNA damage site. Nucleic. Acids. Res., 32, 263-270 (2004).

10.      Budworth, H., Matthewman, G., O'Neill, P. and Dianov, G.L. Repair of tandem lesions in DNA by human cell extracts generates persisting single-strand breaks. J. Mol. Biol., 351, 1020-1029 (2005)

11.      Lomax, M.E., Salje, H., Cunniffe, S. and O'Neill, P. 8-OxoA inhibits the incision of an AP-site by the DNA glycosylases Fpg, Nth, and the AP endonuclease HAP1. Rad. Res. 163, 79-84 (2005).

12.      D. Angelov, V. A. Bomdarenko, S. Almagro, H. Menoni, F. Mongelard, F. Hans, F. Mietton, V. M. Studitsky, A. Hamiche, S. Dimitrov, P. Bouvet Nucleolin is a histone chaperone that possesses FACT-like activity and assists the remodelling of conventional and macroH2A variant nucleosomes. EMBO J., in press (2006).

13.      Chatgilialoglu, C.; Navacchia, M. L.; Postigo, A.. A facile one-pot synthesis of 8-oxo-7,8-dehydro-(2'-deoxy)adenosine in water. Tetrahedron Lett. 47, 711–714 (2006)

14.      Clemens Haas, J. Carsten Pieck, David Kuch, Friederike Grolle, Uwe Linne, and Thomas Carell. PNA Based Reagents for the Direct and Site Specific Synthesis of Thymine Dimer Lesions in DNA, J. Am. Chem. Soc. in press.

15.      Matthias Ober, Heiko Müller, Carsten Pieck, Johannes Gierlich and Thomas Carell. Base Pairing and Replicative Processing of the Formamidopyrimidine-dG DNA Lesion. J. Am. Chem. Soc. 127, 18143-18149 (2005)

16.      Chatgilialoglu, C.; Caminal C.; Guerra, M.; Mulazzani, Q. G.. Tautomers of One-Electron Oxidized Guanosine Angew. Chem. Int. Ed. 44, 6030–6032 (2005)

17.      Gasparutto D., Cognet S., Roussel S. & Cadet J, Synthesis of a convenient thymidine glycol phosphoramidite monomer and its site-specific incorporation into DNA fragments, Nucleosides, Nucleotides and Nucleic Acids, 24, 1831-1842 (2005).

18.      N. Belmadoui, S. Encinas, M. J. Climent, S. Gil, M. A. Miranda. Intramolecular interactions in the triplet excited states of benzophenone-thymine dyads. Chem. Eur. J. 12, 553 (2006).

19.      V. Lhiaubet-Vallet, S. Encinas, M. A. Miranda. Excited state enantiodifferentiating interactions between a chiral benzophenone derivative and nucleosides. J. Am. Chem. Soc. 127, 12774 (2005).

20.      S. Encinas, M. J. Climent, N. Belmadoui, M. A. Miranda. Stereodifferentiation in the excited state behaviour of naphthalene-thymine dyads. Chem. Commun. 2572 (2005).

Joint publications and communications to Conferences produced as a result of these efforts:

1.          The photochemistry of 8-Bromo-2'-deoxyadenosine. A direct entry to cyclopurine lesions. Jimenez, L. B.; Encinas, S.; Miranda, M. A.; Navacchia, M. L.; Chatgilialoglu, C. Photochem. Photobiol. Sci. 3, 1042-1046 (2004).

2.          Independent Generation of Guanosine Base Radicals Vrantza, D.; Gimisis, T.; Vougioukalakis, G.; Orfanopoulos, M.; Encinas, S.; Miranda, M. A.; Gasparutto, D.; Cadet, J. 9th International Symposium on Organic Free Radicals, Porto Vecchio, Corsica, France. June 6-11, 2004.

3.          Photogeneration and Reactivity of 2´-deoxyadenosin-5´-yl Radical. Jimenez, L. B.; Encinas, S.; Miranda, M. A.; Navacchia, M. L.; Chatgilialoglu, C. 13èmes Journées Franco-Espagnoles de Chimie Organique Carry-le Rouet, France. May 23-28 2004.

4.          Manetto, A.; Breeger, S.; Chatgilialoglu, C.; Carell, T. Complex Sequence Dependence by Excess Electron Transfer through DNA with Different Strength Electron Acceptors, Angew. Chem. Int. Ed. 45, 318–321 (2006).

5.          Navacchia, M. L.; Manetto, A.; Montevecchi, P. C.; Chatgilialoglu, C. Eur. J. Org. Chem. 4640–4648 (2005)

6.          Russo, M.; Jimenez, L. B.; Mulazzani, Q. G.; D'Angelantonio, M.; Guerra, M.; Miranda, M. A.; Chatgilialoglu, C.. Chemical Radiation Studies of 8-Bromo-2'-deoxyinosine and 8-Bromoinosine in Aqueous Solutions, Chem. Eur. J. 2006, in press