Figure 1. A) Sequence analysis of a palindromic junction: The native sequence prior to DNA double strand break (DSB) induction (top row), the deduced sequence of the palindromic junction obtained by sodium bisulfite sequencing (middle), and the fold-back priming event presumed to have taken place to produce the palindromic junction (bottom). B) Model for intrachromosomal palindrome formation. After the introduction of a DSB, exonucleolytic processing of the ends reveals a short hairpin that can fold back intramolecularly and prime new DNA synthesis. The remaining broken end can invade the other end via short dispersed inverted repeats, leading to break-induced replication (BIR) that proceeds around the newly created hairpin end, thus duplicating the sequence as a palindrome. Holliday junction resolution of the BIR intermediate leads to a long intrachromosomal palindromic duplication. The palindrome can then extrude into a cruciform, triggering a new DSB, initiating a new cycle of amplification (not shown). Gray arrows indicate extent of duplication. Note that if the other broken arm of the chromosome were to experience fold-back priming instead, this would lead to a hairpin-capped chromatid, which upon replication would resemble a sister chromatid fusion event (a common cytological observation in cells undergoing amplification). Cen and tel refer to centromeric and telomeric regions of the chromosome, respectively.