The study investigates the mechanism by which mitotic chromosome segregation errors lead to DNA breaks and chromosome pulverization, potentially contributing to tumorigenesis. Researchers found that micronuclei, which form when lagging chromosomes are partitioned into micronuclei during mitosis, undergo defective and asynchronous DNA replication, leading to DNA damage and chromosome pulverization. This damage can persist over several generations, and the chromosomes in the micronuclei can be distributed to daughter nuclei, potentially integrating mutations and rearrangements into the genome. The findings suggest that chromosome pulverization may explain "chromothripsis," a phenomenon where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement, contributing to cancer and developmental disorders. The study also highlights the role of micronuclei in promoting DNA damage and the potential for chromothripsis as an extreme outcome of mutagenesis mechanisms in human cancer.The study investigates the mechanism by which mitotic chromosome segregation errors lead to DNA breaks and chromosome pulverization, potentially contributing to tumorigenesis. Researchers found that micronuclei, which form when lagging chromosomes are partitioned into micronuclei during mitosis, undergo defective and asynchronous DNA replication, leading to DNA damage and chromosome pulverization. This damage can persist over several generations, and the chromosomes in the micronuclei can be distributed to daughter nuclei, potentially integrating mutations and rearrangements into the genome. The findings suggest that chromosome pulverization may explain "chromothripsis," a phenomenon where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement, contributing to cancer and developmental disorders. The study also highlights the role of micronuclei in promoting DNA damage and the potential for chromothripsis as an extreme outcome of mutagenesis mechanisms in human cancer.