Figure 3

Genomic rearrangement mechanisms. a. (Adapted from [66]) Non-homologous end-joining (NHEJ) in vertebrates. A double-stranded DNA break (DSB) occurs and is repaired via NHEJ mechanism. The two thick lines depict two DNA strands with DSB, the thin segments in the middle represent the modifications which the ends have gone through before the final ligation. The enzyme machineries catalyzing each step are briefly summarized. They are described in details in references [65] and [70]. Note at step 3 that in order to repair ends, some addition or deletion of bases may be required, leaving behind a 'signature' of NHEJ. b. (Adapted from [82]) After the original stalling of the replication fork (dark blue and red, solid lines), the lagging strand (red, dotted line) disengages and anneals to a second fork (purple and green, solid lines) via microhomology (1), followed by (2) extension of the now 'primed' second fork and DNA synthesis (green, dotted line). After the fork disengages (3), the tethered original fork (dark blue and red, solid lines) with its lagging strand (red and green, dotted lines) could invade a third fork (gray and black, solid lines). Dotted lines represent newly synthesized DNA. Serial replication fork disengaging and lagging strand invasion could occur several times (e.g. FoSTeS x 2, FoSTeS x 3, ... etc.) before (4) resumption of replication on the original template.