Induced detachment of acentric chromatin from mitotic chromosomes leads to their cytoplasmic localization at G(1) and the micronucleation by lamin reorganization at S phase

摘要

Acentric and atelomeric double minute chromatin found in human cancer cells are eliminated from cells by selective incorporation into the micronuclei, We showed previously that most of the micronuclei were formed at S phase and mediated by the nuclear bud-shaped structures that selectively entrap double minutes, In this paper, we have examined the behavior of double minutes in relation to the nuclear lamin protein in cell cycle-synchronized human COLO 320DM tumor cells. At the G(1) phase, we observed that a portion of double minutes was localized at the cytoplasm and showed no association with lamin, The frequency of this localization was increased by hydroxyurea, an inducer of micronuclei, if treated at the preceding S phase. The acentric double minutes were normally segregated to daughter cells by attaching to the mitotic chromosomes, and the hydroxyurea-treatment induced their detachment, possibly through the introduction of the double strand break. When the cells entered S phase, our data suggested that the lamin protein accumulated around the cytoplasmic double minutes at the proximity of the nucleus leading to the formation of the nuclear bud-shaped structure and the initiation of DNA replication. This association of cytoplasmic double minutes with lamin coincided with the large-scale rearrangement of the intranuclear lamin protein, The implication of these findings as well as their application to a broad spectrum of other acentric, atelomeric and autonomously replicating molecules are discussed. [References: 35]