Fig. 6: Scar-prone and scar-free ecDNA formation.
From: Modern biology of extrachromosomal DNA: A decade-long voyage of discovery
a ecDNA formation with a scar on the chromosome. A chromosome undergoes mild DNA damage, such as two DNA double-strand breaks within a certain distance, releasing a linear DNA fragment. The broken chromosome and the free DNA fragment are re-ligated via end-joining individually, forming a circular ecDNA and a repaired chromosome with a focal deletion (scar). b ecDNA formation with multiple scars on the chromosome. A chromosome undergoes pulverization during chromothripsis, resulting in many DNA fragments. Some fragments ligate with each other to form ecDNA, while others reassemble into a heavily rearranged chromosome with multiple scars. c ecDNA formation without a scar on the chromosome. If mild DNA damage occurs in the replication forks during the S phase, the broken chromosome can be repaired by homologous recombination, leaving no scar on the chromosome while an ecDNA forms. d Another possible way to generate ecDNA without leaving a scar on the chromosome. Whole-chromosome or whole-genome duplication occurs before one of the chromosomes shatters. While the broken chromosome is depleted, ecDNA can arise from the fragmentized DNA, resulting in no visible scar on the chromosome.
