Figure 5.

Staggered double-strand DNA cleavage model of CSR. Two S regions indicated by ovals on double-stranded DNA (thick lines) are shown at the top with 5′ and 3′ polarity markers. Bumps on the thick lines indicate stem-loop structure induced by active transcription. The scissors represent a putative endonuclease that cleaves the stem-loop structure and produces staggered nicks in S regions. When 5′ overhang is generated (middle left), it may be double-stranded by error-prone polymerase(s), which introduces mutations and duplication. When a 3′ overhang is produced (middle right), chewing of the overhang by some exonucleases (pacman) will result in deletion. Note that fill-in and chewing are not mutually exclusive. The repaired ends are ligated by the nonhomologous end-joining (NHEJ) system. The ends of the middle segment are self-ligated to form circular DNA (bottom right). The outer segments are ligated to form the chromosomal junction (red arrowhead).