**2. DNA destabilizing compounds**

Stability of DNA double helix is mainly due to reversible non-covalent hydrogen bonds between Watson-Crick base-pairs. Local or global denaturation (melting or breathing) of the double-stranded DNA (dsDNA) helix is dispensable for different cellular processes: DNA replication, transcription and repair (Choi et al., 2004; Schneider et al., 2001). DNA melting is affected by sequence (AT- or GC-rich portions, some successive base pairs arrangements) and their specific tilt, roll, twist effects (Benham, 1996; Dornberger et al., 1999; Krueger et al., 2006), the formation of local hairpins, 3D structures at terminal regions of the DNA helix (Putnam et al., 1981) or internal portions of B- to Z-DNA transition (Harvey, 1983). Such locally opened sites are good substrates for, or are generated by, some cellular proteins: DNA helicases (Betterton & Julicher, 2005), single strand binding proteins (SSBP) such as replication protein A (RPA) (Wold, 1997), UP1 and myeloma helix-destabilizing protein (Herrick & Alberts, 1976; Planck & Wilson, 1980), GAPDH-related protein P8 (Karpel & Burchard, 1981), High Mobility Group (HMG) proteins (Butler et al., 1985), c-Abl kinase (David-Cordonnier et al., 1998, 1999), HIV-1 nucleocapsid protein (Narayanan et al., 2006), prion protein (Bera et al., 2007), NF-B transcription factor (Mura & McCammon, 2008) and UHRF-1 protein (Arita et al., 2008). Besides large DNA opening, small modifications such as base flipping locally perturb DNA stability (Hornby & Ford, 1998) during mismatches or repair proteins interaction from NER (Cao et al., 2004), BER (Bellamy et al., 2007; Tubbs et al., 2007) or DNA methylases/demethylases (Sundheim et al., 2008).

Besides naturally occurring DNA breathing, unzipping is induced by clinically used or potential anti-tumor compounds. The vast majority of DNA-interacting compounds stabilize the DNA double helix; only a very few of them displays the pecular ability to destabilize DNA helix. In this latter group, most belong to DNA intercalating or alkylating families.
