DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe

Uemura, Tadashi; Ohkura, Hiroyuki; Adachi, Yasuhisa; Morino, Kazuhide; Shiozaki, Kazuhiro; Yanagida, Mitsuhiro

doi:10.1016/0092-8674(87)90518-6

Cited by 661 publications

(426 citation statements)

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“…As has been shown in several experimental systems, topo 11 is essential for chromosome condensation and segregation during mitosis as well as during meiosis [31,[33][34][35][36][37][38][39][40][41][42][43]. It is one of the characteristics of Xenopus development that during the early, rapid embryonic cleavages there is almost no transcriptional activity.…”

Section: Discussionmentioning

confidence: 99%

DNA Topoisomerase II Is Not Detectable on Lampbrush Chromosomes but Enriched in the Amplified Nucleoli of Xenopus Oocytes

Fischer

Hock

Scheer

1993

Experimental Cell Research

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In somatic cells DNA topoisomerase 11 (topo 11) is thought to be involved in the domain organization of the genome by anchoring the basis of chromatin loops to a chromosomal scaffold. Lampbrush chromosomes of amphibian oocytes directly display this radial loop organization in cytological preparations. In order to find out whether topo 11 may play a role in the organization of these meiotic chromosomes, we performed immunofluorescence studies using antibodies against Xenopus topo 11. Our results indicate that topo 11 is apparently absent from lampbrush chromosomes and is hence unlikely to act as a "fastener" of the numerous lateral chromosomalloops. Topo 11 was, however, enriched in the amplified nucleoli of Xenopus oocytes. © 1993 Academic Press, Inc. INTRODUCTIONThe chromatin fiber of eukaryotic cells is folded into a series of loops or domains which are stabilized by a structural framework called nuclear matrix or chromosomal scaffold. The loops are thought to be anchored at their base to the matrix or scaffold via specific attachment sites, the so-called matrix or scaffold attachment regions (MARs or SARs). Loop length is variable, ranging from 5 to 200 kbp of DNA [for reviews see 1, 2]. Unfortunately, the chromatin loop structures cannot be directly visualized in interphase nuclei with cytological methods because the chromatin strands are highly entangled.The situation is different for amphibian lampbrush chromosomes which can be readily examined under almost native conditions by light microscopy [3]. The structural organization of these meiotic chromosomes exhibits a striking similarity to the loop model described above. Each lampbrush chromosome consists of a chromosomal axis from which numerous loops radiate laterally. The axis represents a linear array of chromo-1 To whom correspondence and reprint requests should be addressed at Zoologie I, Biozentrum Am Hubland, D-97074 Wiirzburg, Germany. Fax: 0049 931 888 4252. 255 meres containing highly condensed chromatin, while the lateral loops consist of decondensed, transcriptionally active chromatin covered with numerous nascent transcripts. Because lampbrush chromosome architecture resembles so closely the proposed organization of somatic interphase chromatin and mitotic chromosomes, it is tempting to speculate that the same molecular components might be involved in the maintenance of chromatin loops.One of the best characterized components of the chromosomal scaffold is DNA topoisomerase 11 (topo 11) [4][5][6][7]. Besides its enzymatic activity that creates transient double-strand breaks in duplex DNA and passes DNA strands through one another, the protein has been shown to interact with the MAR and SAR elements [8]. Thus, topo 11 is thought to have catalytic as well as structural functions. Topo 11 is not only associated with the scaffold of mitotic chromosomes but also the cores and centromeric regions of spermatocyte-derived meiotic chromosomes [9]. Recently Luke and Bogenhagen identified by biochemical means topo 11 in the germinal vesicles of Xenopus o...

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Section: Discussionmentioning

confidence: 99%

DNA Topoisomerase II Is Not Detectable on Lampbrush Chromosomes but Enriched in the Amplified Nucleoli of Xenopus Oocytes

Fischer

Hock

Scheer

1993

Experimental Cell Research

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“…Decatenation by topo II continues until the onset of anaphase, and the poleward forces on the chromatids may be required to drive decatenation to completion (Holm et al, 1985;Marians, 1987;Uemura et al, 1987;Shamu and Murray, 1992). The decatenation checkpoint therefore monitors the approach to completion, not the full completion, of chromosome disentanglement (Downes et al, 1994).…”

Section: Molecular Mechanism Of the Decatenation Checkpointmentioning

confidence: 99%

The decatenation checkpoint

Damelin

Bestor

2007

Br J Cancer

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The decatenation checkpoint delays entry into mitosis until the chromosomes have been disentangled. Deficiency in or bypass of the decatenation checkpoint can cause chromosome breakage and nondisjunction during mitosis, which results in aneuploidy and chromosome rearrangements in the daughter cells. A deficiency in the decatenation checkpoint has been reported in lung and bladder cancer cell lines and may contribute to the accumulation of chromosome aberrations that commonly occur during tumour progression. A checkpoint deficiency has also been documented in cultured stem and progenitor cells, and cancer stem cells are likely to be derived from stem and progenitor cells that lack an effective decatenation checkpoint. An inefficient decatenation checkpoint is likely to be a source of the chromosome aberrations that are common features of most tumours, but an inefficient decatenation checkpoint in cancer stem cells could also provide a potential target for chemotherapy.

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“…Cells are stained by DAPI for DNA and anti-tubulin antibodies for spindle. By way of comparison, a top2 mutant cell which is defective in condensation and separation is shown (Uemura et al 1987). (Zou et al 1999;Nagase et al 1996) Yamada et al 1997) in a manner which resembles highly that of mitotic cyclins (Funabiki et al 1996a(Funabiki et al , 1997.…”

Section: Fission Yeast Cut2/securin Degrades In Anaphasementioning

confidence: 99%

Cell cycle mechanisms of sister chromatid separation; Roles of Cut1/separin and Cut2/securin

Yanagida

2000

Genes to Cells

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103

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The correct transmission of chromosomes from mother to daughter cells is fundamental for genetic inheritance. Separation and segregation of sister chromatids in growing cells occurs in the cell cycle stage called`anaphase'. The basic process of sister chromatid separation is similar in all eukaryotes: many gene products required are conserved. In this review, the roles of two proteins essential for the onset of anaphase in ®ssion yeast, Cut2/securin and Cut1/separin, are discussed with regard to cell cycle regulation, and compared with the postulated roles of homologous proteins in other organisms. Securin, like mitotic cyclins, is the target of the anaphase promoting complex (APC)/cyclosome and is polyubiquitinated before destruction in a manner dependent upon the destruction sequence. The anaphase never occurs properly in the absence of securin destruction. In human cells, securin is an oncogene. Separin is a large protein (MW <180 kDa), the C-terminus of which is conserved, and is thought to be inhibited by association with securin at the nonconserved N-terminus. In the budding yeast, Esp1/separin is thought to be a component of proteolysis against Scc1, an essential subunit of cohesin which is thought to link duplicated sister chromatids up to the anaphase. Whether ®ssion yeast Cut1/separin is also implicated in proteolysis of cohesin is discussed.

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DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe

Cited by 661 publications

References 29 publications

DNA Topoisomerase II Is Not Detectable on Lampbrush Chromosomes but Enriched in the Amplified Nucleoli of Xenopus Oocytes

DNA Topoisomerase II Is Not Detectable on Lampbrush Chromosomes but Enriched in the Amplified Nucleoli of Xenopus Oocytes

The decatenation checkpoint

Cell cycle mechanisms of sister chromatid separation; Roles of Cut1/separin and Cut2/securin

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