Figure 4.

DNA amplification arising by breakage‐fusion‐bridge (BFB) cycles. Cycle 1 initiates with chromosome breakage (A), occurring for example at a fragile site, or functionally emulated by critically shortened telomere sequences. Following chromosome replication in S‐phase to form sister chromatids (B), the break can be repaired (via NHEJ) by sister chromatid fusion (C). The resultant dicentric chromosome forms an anaphase bridge (D) when the two centromeres are pulled to opposite spindle poles, ultimately resolved by random chromosome breakage (E). The resultant broken chromosome provides a starting point for a subsequent BFB cycle. The blue arrowhead denotes a DNA segment residing proximal to the breakpoint, which becomes duplicated (note inverted structure) following the BFB cycle. Each subsequent BFB cycle can lead to additional duplication (cycle 2 product shown in (F)), resulting in an array of amplified DNA with characteristic inverted repeat architecture. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)