Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA topoisomerase II (topo II) is required at mitosis in yeast for high chromosome condensation and for chromosome segregation. Recent studies on intact mammalian cells using topo II inhibitors that do not stabilize cleavable complexes also suggest a requirement for topo II for complete chromosome condensation and perhaps also for entry into mitosis. We have investigated the effects of merbarone, ICRF-187, and aclarubicin, three topo II inhibitors that do not stabilize the cleavable complex, on entry into mitosis and on chromosome condensation in BHK and in tsBN2 cells. We have compared their effects with those of etoposide, a topo II inhibitor that stabilizes the cleavable complex. All inhibitors induced a concentration-dependent G2 delay or arrest that could be overcome with fostriecin or okadaic acid or by inactivation of RCC1 in tsBN2 cells. Mitotic chromosomes from cells treated with etoposide were extensively fragmented, whereas mitotic chromosomes from cells treated with merbarone, ICRF-187, or aclarubicin were intact but elongated and tangled. These results provide strong evidence that topo II activity is required in chromosome condensation for final coiling of the chromatids. Our results also indicate that protein phosphatases and RCC1 play a role in G2 delay induced by all inhibitors, whether they do or do not stabilize the cleavable complex.
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PMID:Topoisomerase II inhibitors affect entry into mitosis and chromosome condensation in BHK cells. 878 36

Two different type II topoisomerases are known in bacteria. DNA gyrase (Gyr) introduces negative supercoils into DNA. Topoisomerase IV (Par) relaxes DNA supercoils. GyrA and ParC subunits of bacterial type II topoisomerases are involved in breakage and reunion of DNA. The spatial structure of the C-terminal fragment in GyrA/ParC is not available. We infer homology between the C-terminal domain of GyrA/ParC and a regulator of chromosome condensation (RCC1), a eukaryotic protein that functions as a guanine-nucleotide-exchange factor for the nuclear G protein Ran. This homology, complemented by detection of 6 sequence repeats with 4 predicted beta-strands each in GyrA/ParC sequences, allows us to predict that the GyrA/ParC C-terminal domain folds into a 6-bladed beta-propeller. The prediction rationalizes available experimental data and sheds light on the spatial properties of the largest topoisomerase domain that lacks structural information.
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PMID:C-terminal domain of gyrase A is predicted to have a beta-propeller structure. 1194 80