Untangling the role of DNA topoisomerase II in mitotic chromosome structure and function

BioEssays ◽  
1997 ◽  
Vol 19 (2) ◽  
pp. 97-99 ◽  
Author(s):  
Peter E. Warburton ◽  
William C. Earnshaw
1988 ◽  
Vol 24 (11) ◽  
pp. 1783-1790 ◽  
Author(s):  
Erasmus Schneider ◽  
Sandra J. Darkin ◽  
Penelope A. Lawson ◽  
Lai-Ming Ching ◽  
Raymond K. Ralph ◽  
...  

2003 ◽  
Vol 163 (5) ◽  
pp. 937-947 ◽  
Author(s):  
Hong-Guo Yu ◽  
Douglas E. Koshland

Condensin is an evolutionarily conserved protein complex that helps mediate chromosome condensation and segregation in mitotic cells. Here, we show that condensin has two activities that contribute to meiotic chromosome condensation in Saccharomyces cerevisiae. One activity, common to mitosis, helps mediate axial length compaction. A second activity promotes chromosome individualization with the help of Red1 and Hop1, two meiotic specific components of axial elements. Like Red1 and Hop1, condensin is also required for efficient homologue pairing and proper processing of double strand breaks. Consistent with these functional links condensin is necessary for proper chromosomal localization of Red1 and Hop1 and the subsequent assembly of the synaptonemal complex. Finally, condensin has a Red1/Hop1-independent role in the resolution of recombination-dependent linkages between homologues in meiosis I. The existence of distinct meiotic activities of condensin (axial compaction, individualization, and resolution of recombination-dependent links) provides an important framework to understand condensin's role in both meiotic and mitotic chromosome structure and function.


Author(s):  
Manuel Luis Orta ◽  
Inmaculada Domínguez ◽  
Nuria Pastor ◽  
Felipe Cortés ◽  
Santiago Mateos

2000 ◽  
Vol 11 (4) ◽  
pp. 1293-1304 ◽  
Author(s):  
Brigitte D. Lavoie ◽  
K. Michelle Tuffo ◽  
Scott Oh ◽  
Doug Koshland ◽  
Connie Holm

In vitro studies suggest that the Barren protein may function as an activator of DNA topoisomerase II and/or as a component of theXenopus condensin complex. To better understand the role of Barren in vivo, we generated conditional alleles of the structural gene for Barren (BRN1) in Saccharomyces cerevisiae. We show that Barren is an essential protein required for chromosome condensation in vivo and that it is likely to function as an intrinsic component of the yeast condensation machinery. Consistent with this view, we show that Barren performs an essential function during a period of the cell cycle when chromosome condensation is established and maintained. In contrast, Barren does not serve as an essential activator of DNA topoisomerase II in vivo. Finally,brn1 mutants display additional phenotypes such as stretched chromosomes, aberrant anaphase spindles, and the accumulation of cells with >2C DNA content, suggesting that Barren function influences multiple aspects of chromosome transmission and dynamics.


1992 ◽  
Vol 70 (5) ◽  
pp. 354-364 ◽  
Author(s):  
Abdul M. Deffie ◽  
J. Peter McPherson ◽  
Radhey S. Gupta ◽  
David W. Hedley ◽  
Gerald J. Goldenberg

The role of DNA topoisomerase II in multifactorial resistance to antineoplastic agents is reviewed. We have previously observed that in Adriamycin (ADR) resistant P388 murine leukemia cells, DNA topoisomerase II enzyme content and cleavage and catalytic activities were all reduced and correlated with drug sensitivity. A subsequent study provided evidence for an allelic mutation of the gene for DNA topoisomerase II as a possible molecular mechanism underlying the enzyme alterations. To ascertain how universal were these observations, a study was undertaken of DNA topoisomerase II (topo II) in other cell lines resistant either to ADR or another topo-II-interactive drug, mitoxantrone. In ADR-resistant Chinese hamster ovary (CHO) cells, topo II cleavage and catalytic activities and the gene product were all reduced; however, only cleavage activity correlated with drug sensitivity. No differences were noted between ADR-sensitive and -resistant CHO cells by Northern or Southern blot analysis, raising the possibility that the enzyme in resistant cells may be regulated at a posttranscriptional level. Findings on a gel retardation or immunoblot band depletion assay showed that the enzyme in CHO/ADR-1 cells failed to bind to the DNA–drug–enzyme complex, suggesting a qualitative as well as quantitative enzyme alteration in those cells. Mitoxantrone-resistant HeLa cells (Mito-1) displayed not only a lower level of cleavage activity but also of enzyme content and catalytic activity, relative to the parental drug-sensitive HeLa cells. As with the CHO cells, no differences were noted between mitoxantrone-sensitive and -resistant HeLa cells on Northern and Southern blot analyses, suggesting that enzyme regulation in these resistant cells may also be at a posttranscriptional level. There was no evidence of enzyme binding to DNA–drug–enzyme complex in resistant HeLa/Mito-1 cells, once again suggesting the presence of a qualitative enzyme alteration. The findings in both ADR-resistant CHO cells and mitoxantrone-resistant HeLa cells do not exclude the possibility that subtle changes in the topoisomerase II gene, such as point mutations, may account for these enzyme changes. The apparent qualitative changes observed in enzyme may result from posttranslational modifications such as phosphorylation.Key words: drug resistance, DNA topoisomerase II, Adriamycin, mitoxantrone.


1987 ◽  
Vol 36 (20) ◽  
pp. 3477-3486 ◽  
Author(s):  
Yves Pommier ◽  
Joseph Covey ◽  
Donna Kerrigan ◽  
William Mattes ◽  
Judith Markovits ◽  
...  

Author(s):  
M D'Andrea ◽  
P Farber ◽  
D Foglesong

DNA topoisomerases are enzymes which insert transient breaks into duplex DNA and are important in DNA replication, transcription and recombination. There are two forms of the enzyme, Topoisomerase I which breaks and rejoins only one of the two strands of DNA and Topoisomerase II (Topo II) which breaks and rejoins both of the DNA duplex strands. The essential role of Topo II in cell proliferation is reflected in its abundance in dividing cells, including normal and neoplastic cells.


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