Figure 6

Possible mechanisms for formation of G and S phase DDJ. Steps 1 and 2 illustrate an inverted FAP. When the DNA in Step 1 is bent 180°, the two Alu elements within the inverted FAP are aligned. Steps 3A-6A and 3B-6B illustrate two possible mechanisms for interactions between inverted Alu elements without the formation of a hairpin loop. Steps 3A-6A, DNA Breathing (G phase) Mediated APE deletion. (3A) DNA breathing bubbles are typically < 20 bp [45] and are characterized by flipping of the unpaired nucleotide bases away from the center line of the double-helix [37]. A bubble in this conformation could be susceptible to interaction with a bubble of similar sequence. (4A) Simultaneous bubbles may arise in identical sections of aligned Alu elements. (5A) Simultaneous homologous bubble alignment could initiate bubble-bubble interaction with the potential for forming a 'double-bubble' conformation. (6A) The ectopic formation of the double-bubble conformation within two aligned breathing bubbles could potentially extend to the entire length of the two aligned Alu elements. The high GC content of Alu elements would likely increase the stability of the hypothesized doomsday junction. DDJs likely possess four single-stranded sections of single-stranded DNA at each end which could be susceptible to single-strand nuclease attack. Steps 3B-6B, Replication Fork (S phase) Mediated APE Deletion 3B-5B) Initiation and growth of a replication bubble. (5B) Coincident progression of the DNA replication bubble through an inverted FAP. (6B) Invasion and ectopic annealing of high-homology replication forks. APE: Alu pair exclusion; DDJ: doomsday junction; FAP: full-length Alu pair.