Chromothripsis from Ruptured Micronuclei. When a chromosome mis-segregates during mitosis, it can result in a daughter cell with two nuclei, the primary nucleus (PN) containing most of the genome and the micronucleus (MN), containing the missegregated chromatin (upper-left). After the cell enters S phase, DNA replication can occur on the micronucleated chromatin (upper-right). Rupture of the nuclear envelope during replication (middle-left) causes DNA damage, including double-stranded DNA breaks (middle-right). When the damaged chromatin is re-enclosed in a nuclear envelope after mitosis, DNA damage repair pathways can recognize the shattered chromatin and randomly reassemble the pieces to form a new chromosome (lower-right).Reprinted from Cell, Vol 161, Hatch EM and Hetzer MW, Linking Micronuclei to Chromosome Fragmentation, Pages No. 1502-1504, Copyright 2015, with permission from Elsevier.