Helix invasion

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). 

ATPase family. To accomplish the exchange, the single-stranded DNA displaces one of the strands of the double helix (Figure 28.48). The resulting three-stranded structure is called a displacement loop or D loop. This process is often referred to as strand invasion. Because a free 3 end is now bound to a contiguous strand of DNA, the 3 end can act as a primer to initiate new DNA synthesis. Strand invasion can initiate many processes, including the repair of double-stranded breaks and the reinitiation of replication after the replication apparatus has come off its template. In the repair of a break, the recombination partner is an intact DNA molecule with an overlapping sequence. 

Recombination is the exchange of segments between two DNA molecules. Recombination is important in some types of DNA repair as well as other processes such as meiosis, the generation of antibody diversity, and the life cycles of some viruses. Some recombination pathways are initialed by strand invasion, in which a single strand at the end of a DNA double helix forms base pairs with one strand of DNA in another double helix and displaces the other strand. A common intermediate formed in other recombination pathways is the Holliday junction, which consists of four strands of DNA that come together to form a crosslike structure. Recoinbinases promote recombination reactions through the introduction of specific DNA breaks and the formation and resolution of junction intermediates. 

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