Double duplex invasion

Fig. 4.4 Double duplex invasion of pseudo complementary PNAs. In order to obtain efficient binding, the target (and thus the PNAs) should contain at least 50% AT (no other sequence constraints), and in the PNA oligomers all A/T base pairs are substituted with...

Triplex Triplex Invasion Duplex Invasion Double Duplex Invasion Tail-Ciamp... 

PNA targeting of duplex DNA is not limited to homopurine sequences. Under special circumstances (high negative superhelical stress) mixed purine-pyrimidine PNA-peptide conjugates can bind by duplex invasion (Fig. 4.7) [31], but such complexes are of limited stability. However, using a set of pseudo-complementary PNAs containing diaminopurine-thiouracil substitutions, very stable double duplex invasion complexes can be formed (Fig. 4.4) and the only sequence requirement is about 50% AT content. Very recently, it was also demonstrated that reasonably stable helix invasion complexes can be obtained with tail-clamp PNA comprising a short (>six bases) homopyrimidine bis-PNA clamp and a mixed sequence tail extension [32] (Fig. 4.7). 

Lohse j., Dahl O., Nielsen P.E. Double duplex invasion by peptide nucleic acid a general principle for sequence-specific... 

Lohse J, Dahl O, Neilsen PE (1999) Double duplex invasion by peptide nucleic acid a general principle for sequence-specific targeting of double stranded DNA. Proc Natl Acad Sci USA 96 11804-11808 Lonn U, Lonn S, Nylen U, Windblad G (1990) Bleomycin-induced DNA lesions are dependent on nucleosome repeat length. Biochem Pharmacol 39(1) 101-107 Lopez-Larraza DM, Bianchi NO (1993) DNA response to bleomycin in mammalian cells with variable degrees of chromatin condensation. Environ Mol Mutagen 21(3) 258—264 Lopez-Larraza DM, Padron J, Rond NE, Vidal Rioja LA (2006) Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin. Mutat Res 16 April [Epub ahead of print]... 

Lohse, J., Dahl, O. and Nielsen, P.E. (1999). Double duplex invasion by peptide nucleic acid a general principle for sequence-specific targeting of double-stranded DNA. Proc. Natl. Acad. Sci. USA, 96, 11804-11808. 

Bentin T, Nielsen P.E. Combined tri-plex/duplex invasion of double-stranded DNA by Tail-Clamp peptide nucleic acids (PNA). (Submitted)... 

For the present site-selective scission of double-stranded DNA, both pcPNA additives must have flanking portions so that gap-like structures are formed in the double-stranded DNA. Thus, no site-selective scission was observed when pcPNA 3 and pcPNA 4 were combined as additives [Figure 7.10(a), lane 4], These two pcPNAs are completely complementary (their duplex is not much formed due to mutual steric repulsion under the conditions employed), and thus no gap-like structures are produced in the invasion complex [see structure at the bottom of Figure 7.9(a)], No scission occurred in the absence of pcPNA additives, as expected (lane 2). 

Figure 7 Repair of the double-strand break by homologous recombination in mammalian cells. In homologous recombination, an intact homologous chromosome is used to retrieve information and repair double-strand breaks in the duplex. The three basic steps of homologous recombination are strand invasion, branch migration, and Holliday junction formation.

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