Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex
By using tissue miniunits, protein kinase modulators, and topoisomerase inhibitors in short-term incubation (0-90 min) we studied (1) the role of protein phosphorylation in the immediate control of DNA replication in the developing rat cerebral cortex and (2) the mechanism of action for genistein- m...
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todo:paper_00144886_v159_n1_p164_Yakisich2023-10-03T14:12:43Z Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex Yakisich, J.S. Sidén, A. Vargas, V.I. Eneroth, P. Cruz, M. Cerebral cortex DNA synthesis Genistein Protein kinases Protein phosphorylation Topoisomerases calphostin C camptothecin DNA topoisomerase DNA topoisomerase (ATP hydrolysing) DNA topoisomerase inhibitor etoposide genistein herbimycin A phosphoprotein phosphatase inhibitor protein kinase inhibitor staurosporine animal tissue article brain cortex cell cycle S phase controlled study DNA replication DNA synthesis DNA synthesis inhibition enzyme activity enzyme inhibition newborn nonhuman priority journal protein phosphorylation rat By using tissue miniunits, protein kinase modulators, and topoisomerase inhibitors in short-term incubation (0-90 min) we studied (1) the role of protein phosphorylation in the immediate control of DNA replication in the developing rat cerebral cortex and (2) the mechanism of action for genistein- mediated DNA synthesis inhibition. Genistein decreased the DNA synthesis within less than 30 min. None of the other protein kinase inhibitors examined (herbimycin A, staurosporine, calphostin-C) or the protein phosphatase inhibitor sodium orthovanadate inhibited DNA synthesis and they did not affect the genistein-mediated inhibition. The selective topoisomerase inhibitors camptothecin and etoposide decreased the DNA synthesis to an extent similar to that of genistein and within less than 30 min. In addition, the effects of these substances on topoisomerase I and II were studied. Etoposide and genistein but not herbimycin A, staurosporine, or calphostin-C strongly inhibited the activity of topoisomerase II. Our results (1) strongly suggest that the net rate of DNA replication during the S phase of the cell cycle is independent of protein phosphorylation and (2) indicate that the early inhibitory effect of genistein on DNA synthesis is mediated by topoisomerase II inhibition rather than protein tyrosine kinase inhibition. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00144886_v159_n1_p164_Yakisich |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cerebral cortex DNA synthesis Genistein Protein kinases Protein phosphorylation Topoisomerases calphostin C camptothecin DNA topoisomerase DNA topoisomerase (ATP hydrolysing) DNA topoisomerase inhibitor etoposide genistein herbimycin A phosphoprotein phosphatase inhibitor protein kinase inhibitor staurosporine animal tissue article brain cortex cell cycle S phase controlled study DNA replication DNA synthesis DNA synthesis inhibition enzyme activity enzyme inhibition newborn nonhuman priority journal protein phosphorylation rat |
| spellingShingle |
Cerebral cortex DNA synthesis Genistein Protein kinases Protein phosphorylation Topoisomerases calphostin C camptothecin DNA topoisomerase DNA topoisomerase (ATP hydrolysing) DNA topoisomerase inhibitor etoposide genistein herbimycin A phosphoprotein phosphatase inhibitor protein kinase inhibitor staurosporine animal tissue article brain cortex cell cycle S phase controlled study DNA replication DNA synthesis DNA synthesis inhibition enzyme activity enzyme inhibition newborn nonhuman priority journal protein phosphorylation rat Yakisich, J.S. Sidén, A. Vargas, V.I. Eneroth, P. Cruz, M. Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex |
| topic_facet |
Cerebral cortex DNA synthesis Genistein Protein kinases Protein phosphorylation Topoisomerases calphostin C camptothecin DNA topoisomerase DNA topoisomerase (ATP hydrolysing) DNA topoisomerase inhibitor etoposide genistein herbimycin A phosphoprotein phosphatase inhibitor protein kinase inhibitor staurosporine animal tissue article brain cortex cell cycle S phase controlled study DNA replication DNA synthesis DNA synthesis inhibition enzyme activity enzyme inhibition newborn nonhuman priority journal protein phosphorylation rat |
| description |
By using tissue miniunits, protein kinase modulators, and topoisomerase inhibitors in short-term incubation (0-90 min) we studied (1) the role of protein phosphorylation in the immediate control of DNA replication in the developing rat cerebral cortex and (2) the mechanism of action for genistein- mediated DNA synthesis inhibition. Genistein decreased the DNA synthesis within less than 30 min. None of the other protein kinase inhibitors examined (herbimycin A, staurosporine, calphostin-C) or the protein phosphatase inhibitor sodium orthovanadate inhibited DNA synthesis and they did not affect the genistein-mediated inhibition. The selective topoisomerase inhibitors camptothecin and etoposide decreased the DNA synthesis to an extent similar to that of genistein and within less than 30 min. In addition, the effects of these substances on topoisomerase I and II were studied. Etoposide and genistein but not herbimycin A, staurosporine, or calphostin-C strongly inhibited the activity of topoisomerase II. Our results (1) strongly suggest that the net rate of DNA replication during the S phase of the cell cycle is independent of protein phosphorylation and (2) indicate that the early inhibitory effect of genistein on DNA synthesis is mediated by topoisomerase II inhibition rather than protein tyrosine kinase inhibition. |
| format |
JOUR |
| author |
Yakisich, J.S. Sidén, A. Vargas, V.I. Eneroth, P. Cruz, M. |
| author_facet |
Yakisich, J.S. Sidén, A. Vargas, V.I. Eneroth, P. Cruz, M. |
| author_sort |
Yakisich, J.S. |
| title |
Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex |
| title_short |
Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex |
| title_full |
Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex |
| title_fullStr |
Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex |
| title_full_unstemmed |
Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex |
| title_sort |
early effects of protein kinase modulators on dna synthesis in rat cerebral cortex |
| url |
http://hdl.handle.net/20.500.12110/paper_00144886_v159_n1_p164_Yakisich |
| work_keys_str_mv |
AT yakisichjs earlyeffectsofproteinkinasemodulatorsondnasynthesisinratcerebralcortex AT sidena earlyeffectsofproteinkinasemodulatorsondnasynthesisinratcerebralcortex AT vargasvi earlyeffectsofproteinkinasemodulatorsondnasynthesisinratcerebralcortex AT enerothp earlyeffectsofproteinkinasemodulatorsondnasynthesisinratcerebralcortex AT cruzm earlyeffectsofproteinkinasemodulatorsondnasynthesisinratcerebralcortex |
| _version_ |
1782026878688690176 |