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J Comp Neurol. 2005 Dec 19;493(3):357-69.

DNA topoisomerase I in the mouse central nervous system: Age and sex dependence.

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Department of Microbiology & Immunology, the Ben-Gurion University Cancer Research Center, Beer-Sheva 84105, Israel.


Topoisomerase I (topo I) is a nuclear enzyme responsible for the topological state of DNA and therefore participates in most DNA transactions, particularly in transcription. Topo I, a ubiquitous enzyme, was identified and characterized in various cell types and tissues; however, the characterization of topo I in the intact central nervous system was not performed. Here we investigated, for the first time, the activity, level, and distribution pattern of topo I in the various selected brain regions in the mouse. In the visual cortex, cerebellum, and striatum the activity of topo I was 3-4-fold higher compared to that found in the hippocampus and hypothalamus. Immunohistochemical and immunofluorescence analyses revealed specific distribution patterns of topo I protein in neurons of each of the areas examined. The highest topo I levels were observed in inhibitory neurons. In addition to the expected nuclear localization of this protein, some neurons exhibited significant cytoplasmic content as well. The activity and level of topo I is age- and gender-dependent. It increases from birth to maturity and decreases, more significantly in males, with senescence. These results point to a possible importance and involvement of topo I activity and regulation in various brain functions.

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