**3.7 Unwound DNA**

408 DNA Repair

However, mismatch repair proteins are not involved in this TFO-induced mutagenesis. Several reports have now shown that cells that are deficient in the MutS and MutL homologues MSH2, MLH1, MSH3, or MSH6, do not show any change in TFO-induced mutagenesis. In contrasts, NER factors can recognize the intermolecular triplex at least in part. Therefore NER was involved in the triplex-induced mutagenesis and recombination in cells. For example, in *E.coli*, NER proteins, such as UvrB and UvrC, were necessary for H-DNA-induced cell growth retardation and cell lysis, similarly, recombination induced by

G-quadruplexes are higher-order DNA or RNA structures formed from G-rich DNA or RNA sequences that are built around tetrads of hydrogen-bonded guanine bases (Lipps & Rhodes, 2009; Sannohe & Sugiyama, 2010). Despite the wide prevalence of genomic sequences that have G-rich property and that can potentially fold into tetraplex / quadruplexes structures, a direct demonstration of their existence *in vivo* proved to be a difficult undertaking. Only recently has there evidence started to increase for their presence and role *in vivo* (Lipps & Rhodes, 2009), since most of the tetraplex/ quadruplexes forming sequences are fairly short and quadruplexes are likely to be transiently formed. G-quadruplexes (tetraduplex) may have

Recent progress of the related studies revealed that G-quadruple could provide a nucleic acid based mechanism, such as regulating telomere maintenance, transcription, replication as well as translation. In the same time, various G-quadruplexes binding proteins, such as, a G4 quadruplex and purine Motif triplex nucleic acid-binding protein have also been characterized

The existence of cellular proteins that preferentially interact with tetraplex DNA provides a

(Dyke et al.,2004), many others have been summarized in the reference (Fry, 2007).

strong argument for the existence of quadruplex formations in genomic DNA.

several isomers which can be formed intramolecularly and intermolecularly (Fig. 4).

TFOs depends also on the NER pathway (Faruqi et al., 2000).

**3.6 G-tetraduplex and genetic instability** 

Fig. 4. Tetraplex DNA

Unwound DNA is known to be formed by A+T -rich sequences (Fig. 5). Since A· T base pairs contain two hydrogen bonds and C· G base pairs contain three, A· T-rich tracts are less thermally stable than C· G -rich tracts in DNA. In the presence of superhelical energy, A+T rich regions can unwind and remain unwound under conditions normally found in the cell. Such sites often provide places for DNA replication proteins to enter DNA to begin the chromosome duplication. Unwound DNA can therefore be alternatively called as DNA unwinding elements (DUEs) that have been identified in both prokaryotic and eukaryotic DNA sequences. DUEs are AT-rich sequences about 30-100 bp long. They share little sequence similarity except for being AT-rich. Under torsion stress, unwinding of the double helix occurs first in AT-rich sequences; therefore, DUEs can be maintained as unpaired DNA regions in the presence of negative supercoiling. The single-stranded area of the unwound structure may be target of nuclease activity resulting in single or DSBs, leading to enhanced mutagenesis or recombination.

Fig. 5. Unwound DNA
