title: Nuclear envelope-limited chromatin sheets are part of mitotic death.
abstract: Nuclear envelope-limited chromatin sheets (ELCS) are enigmatic membranous structures of uncertain function. This study describes the induction of ELCS in p53 mutated Burkitt's lymphoma cell lines after treatment with irradiation or the microtubule inhibitor, SK&F 96365. Both treatments evoked similar mitotic death, involving metaphase arrest followed by extensive endopolyploidisation and delayed apoptosis, although the kinetics were different. We found that induction of ELCS and nuclear segmentation correlated with the amount and kinetics of M-phase arrest, mitosis restitution and delayed apoptosis of endopolyploid cells. In metaphases undergoing restitution, ELCS are seen participating in the restoration of the nuclear envelope, mediating the attachment of peripheral chromatin to it. In interphase cells, ELCS join nuclear segments, ectopically linking and fusing with heterochromatin regions. In cells with segmented nuclei, continued DNA replication was observed, along with activation and redistribution of Ku70, suggestive of non-homologous DNA end-joining. Induction of ELCS also parallels the induction of cytoplasmic stacked membrane structures, such as confronting cisternae and annulate lamellae, which participate in the turnover and degeneration of ELCS. The results suggest that arrest at a spindle checkpoint and the uncoupling of mitosis from DNA replication lead to the emergence of ELCS in the resulting endopolyploid cells.
authors.affiliation: Laboratory of Tumour Cell Biology, Biomedicine Centre of the Latvian University, Ratsupites str. 1, 1067 Riga, Latvia. cancer@latnet.lv
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Erenpreisa
authors.forename: Andrey
authors.initials: A
authors.lastname: Ivanov
authors.forename: Mark
authors.initials: M
authors.lastname: Cragg
authors.forename: Galina
authors.initials: G
authors.lastname: Selivanova
authors.forename: Timothy
authors.initials: T
authors.lastname: Illidge
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002843:Chromatin / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008854:Microscopy, Electron; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
chemical_list: D002843:Chromatin; D007093:Imidazoles; D004247:DNA; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole