**4. Conclusion**

110 Selected Topics in DNA Repair

disturbed Watson-Crick hydrogen bonding than B[*c*]Ph-dA adducts, in correlation with stronger excision efficiency by NER machinery. The fjord region B[*c*]Ph-dA adducts being poorly excised lead to more tumorigenic activities. HMG-1 and -2 proteins are also implicated in bulky BPDE-adducts recognition (Lanuszewska & Widlak, 2000) but the consequences on repair or cell death are unknown (**3**). HMG binding might protects adduct recognition by repair proteins as for platinated DNA, but this needs further evaluation. Excision of bulky 4-OHEN-DNA adducts by NER proteins also depends on both the nature of the alkylated base, its stereo-isomery and the sequence context. For instance, 4-OHEN-dC adducts are more efficiently excised from the DNA than the 4-OHEN-dA adducts (D. Chen et al., 2006). It was reported in male zebrafish that 17a-ethinylestradiol, as a source of 4- OHEN, induces a decrease in NER activity as part of a decrease of the expression level of some NER genes such as XPC, XPA, XPD and XPF, but not of HR23B (Notch et al., 2007).

DNA alkylation by psoralen can lead to inter-strand crosslinks (ICL) or mono-adducts (MA). Psoralen-ICLs (Figure 9) are eliminated during the replication process, associated with HR (**1**), MMR (**2**) and error-prone translesion DNA polymerases (Dronkert & Kanaar, 2001). NER proteins such as XPC/hHR23B complex and XPA/RPA complexes are also implicated in the repair of psoralen-ICL (Thoma et al., 2005) and could cooperate with MMR to excise the lesions (Zhao et al., 2009). By contrast, thymine-psoralen mono-adducts (**3**) are moderately excised from the DNA by the NER system (Vasquez et al., 2002), because of adduct recognition by HMG-B1 which recruits RPA helicase (**4**) (Lange et al., 2009) or by MMR

**3.5 DNA repair for psoralen-DNA adducts** 

Fig. 9. DNA repair pathways for psoralen-induced DNA damage.

Destabilization of the DNA helix that is induced by drugs is an important aspect of the antitumor mechanism of action of this series of compounds besides they represent just few droplets in an ocean of DNA-interacting compounds that mainly stabilize the double helix. As evidenced here, stabilizing *vs.* destabilizing compounds differs in terms of molecular and cellular processes: DNA repair, transcription or replication. From the different series (platinum, ruthenium, BPDE, benzoacronycines), the level of DNA destabilization correlates with the efficiency of protein recognition and anti-tumor/cytotoxic activities. Therefore, we believe that it is important not to consider DNA destabilization as a unique process but in relation with potential associated bending of the DNA helix (as evidenced using oxaliplatinand cisplatin-induced distortions or the different isomers of BPDE) and with the size of the locally destabilized DNA (for instance, portions of DNA opened by benzoacronycines are strongly sensitive to single-strand-specific nucleases). The most recent and ongoing studies

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