Figure 5

Comparison of non-allelic homologous recombination, non-homologous end-joining and Fork Stalling and Template Switching mechanisms resulting in genomic duplication/deletion. The two thin lines in all three schemes represent the double strands of DNA. Left column: An intrachromatid non-allelic homologous recombination (NAHR) event. Rectangles in different shades of blue depict two directly orientated low-copy reapeats (LCRs) sharing high homology (97% to 98%), which align at non-allelic rather than allelic positions and the subsequent recombination causes deletion or duplication (reciprocal events but not with equivalent frequencies) of part of the two LCRs as well as the segment flanked by them. Middle column: a non-homologous end-joining (NHEJ) event. Double-strand breaks (DSBs) are created between the two sequences represented as a blue and a red rectangle with no homology between each other. The NHEJ system modifies and rejoins the two ends, resulting in the deletion of the segment between the two DSBs. Right column: a Fork Stalling and Template Switching (FoSTeS) × 2 event causing a complex deletion involving two fragments. No extensive homology is required between the substrate sequences depicted by a blue, a red and a green rectangle. However, the small open triangle heading downwards depicts a site bearing microhomology (2 to 5 base pairs) between the blue and the red sequences, and the small filled triangle heading downwards depicts another site bearing microhomology between the red and the green sequences. Different from NAHR and NHEJ, the FoSTeS event occurs during DNA replication. The replication forks from the two surrounding sequences are shown in the same color as the rectangles. The leading nascent strand at the left side (blue or red) fork invades the right side (red or green) fork via the demonstrated microhomology, and primes its own further synthesis using the right side fork as template. This event happens twice, causing deletion of the two fragments flanked by each pair of microhomology sites. Note the juxtaposition of genomic sequences from multiple distinct regions yielding complex rearrangements.