Fig. 1: ecDNA biogenesis, inheritance, and function.

a Chromosoma instability (CIN) promotes extensive chromosome missegregation coupled with the formation of relatively unstable micronuclei. Upon rupture of their envelope, the cytosolic nuclease N4BP2 acquires access to micronuclear DNA, resulting in extensive DNA damage, catastrophic chromatin fragmentation, and the generation of extrachromosomal DNA (ecDNA). b ecDNA persists across cell divisions through epigenetically regulated retention elements that enable tethering to chromosomes. c During interphase, ecDNA integrates into transcriptional condensates via ecDNA-encoded super-enhancers (ecSEs) that preferentially associate with the transcriptional coactivator MED1, reshaping higher-order nuclear architecture and activating oncogenic transcription programs.