Segregation of recombined chromosomes in meiosis I requires DNA topoisomerase II

Rose, David W.; Thomas, Winston; Holm, Connie

doi:10.1016/0092-8674(90)90349-j

Cited by 161 publications

(95 citation statements)

References 30 publications

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“…Unlike spindle inhibitors, the most common class of aneugens, ET induces numerical abnormalities without interacting directly with cellular organelles responsible for chromosome movement (i.e., kinetochores, centromeres, spindle fibers, etc.). ET may prevent the segregation of the homologous chromosomes because topo II is required for the resolution of recombined chromosomes and the proper segregation of sister chromatids (10). Recently, it was reported that ET treatment decreased meiotic recombination frequencies in male germ cells (46).…”

Section: Discussionmentioning

confidence: 99%

“…Topo II enzymes function by transiently introducing DNA double-strand breaks, allowing the passage of one double helix through another, and resealing the double-strand break (8). Topo II activity is needed for removing regions of DNA catenation during DNA replication and before chromosome segregation (9)(10)(11) and for chromosome condensation (12). It is an abundant nuclear protein that is associated with the chromosome core or scaffold of metaphase chromosomes (13,14) and with elements of the synaptonemal complex (15).…”

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Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Marchetti

Bishop

Lowe

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Etoposide, a topoisomerase II inhibitor widely used in cancer therapy, is suspected of inducing secondary tumors and affecting the genetic constitution of germ cells. A better understanding of the potential heritable risk of etoposide is needed to provide sound genetic counseling to cancer patients treated with this drug in their reproductive years. We used a mouse model to investigate the effects of clinical doses of etoposide on the induction of chromosomal abnormalities in spermatocytes and their transmission to zygotes by using a combination of chromosome painting and 4 ,6-diamidino-2-phenylindole staining. High frequencies of chromosomal aberrations were detected in spermatocytes within 64 h after treatment when over 30% of the metaphases analyzed had structural aberrations (P < 0.01). Significant increases in the percentages of zygotic metaphases with structural aberrations were found only for matings that sampled treated pachytene (28-fold, P < 0.0001) and preleptotene spermatocytes (13-fold, P < 0.001). Etoposide induced mostly acentric fragments and deletions, types of aberrations expected to result in embryonic lethality, because they represent loss of genetic material. Chromosomal exchanges were rare. Etoposide treatment of pachytene cells induced aneuploidy in both spermatocytes (18-fold, P < 0.01) and zygotes (8-fold, P < 0.05). We know of no other report of an agent for which paternal exposure leads to an increased incidence of aneuploidy in the offspring. Thus, we found that therapeutic doses of etoposide affect primarily meiotic germ cells, producing unstable structural aberrations and aneuploidy, effects that are transmitted to the progeny. This finding suggests that individuals who undergo chemotherapy with etoposide may be at a higher risk for abnormal reproductive outcomes especially within the 2 months after chemotherapy.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Marchetti

Bishop

Lowe

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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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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“…The tunnel is likely to represent the channel through which one DNA duplex, after capture in the clamp formed by the N-terminal domains, is transferred across the interface between the enzyme's subunits. These images are consistent with biochemical observations and provide a structural basis for understanding the reaction of topoisomerase II. Enzymes of the DNA topoisomerase II family catalyze the transfer of a duplex DNA through a transient gate in another duplex DNA (1)(2)(3)(4)(5) and are implicated in several aspects of the replication and functions of DNA, including the segregation of chromosomes in prokaryotic and eukaryotic cells (6)(7)(8)(9)(10)(11)(12). Biochemical studies of the reaction of eukaryotic topoisomerase II show that the gate in one DNA (the G-segment: refs.…”

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confidence: 99%

Structure and conformational changes of DNA topoisomerase II visualized by electron microscopy.

Schultz

Olland

Oudet

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Segregation of recombined chromosomes in meiosis I requires DNA topoisomerase II

Cited by 161 publications

References 30 publications

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

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

Structure and conformational changes of DNA topoisomerase II visualized by electron microscopy.

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