Origin-Dependent Inverted-Repeat Amplification: A Replication-Based Model for Generating Palindromic Amplicons

(dsDNA) break and implicate DNA fusions (either homologous or non-homologous), Break-Induced Replication (BIR), Microhomology/Microsatellite-Induced Replication (MMIR), and/or inverted or directly repeated sequences that adopt unusual secondary structures for their repair [4]. From the molecular analysis [7] of a yeast strain that contains amplified copies of the gene for the high affinity sulfur transporter, SUL1 [3], we derived a new general model that explains the generation of interstitial tandem inverted repeat arrays of chromosome segments in yeast and in human cancers, and of de novo congenital inverted triplications and other chromosomal rearrangements. We propose that cells commit a singular error in replication: the ligation of the nascent leading strand to the nascent lagging strand at the replication fork. This model can potentially explain the origin of many palindromic rearrangements and their structural, enzymatic, and genetic requirements.