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Synthesis of proteins is absolutely essential for any known form of life. It is carried out by cellular organelles named ribosomes, one of the most incredible cellular machines, frequently referred to as protein factories. The ribosomal RNA (rRNA) is the key building block of the ribosomes and rRNA is essential to both their structure and function. The synthesis of rRNA (also known as transcription) is the key regulator of ribosome production and fundamental to life. The transcription of ribosomal RNA is tightly linked to cell growth and division and when deregulated could have a dramatic effect on the cell s fate, leading to cell death or defects which might result in oncogenic transformation. An elevated level of rRNA synthesis supports the unrestrained proliferation of cancer cells and rRNA transcription therefore represents a valid target for anticancer therapy. In the proposed research, we will use various biochemical approaches to study the mechanism of rRNA transcription and will focus on the role of topoisomerase-II, one of the most amazing enzymes, in the regulation of rRNA transcription in human cells. Topoisomerases, these magicians of DNA world are targets for a number of highly successful anticancer drugs and a key target for development of better therapeutics. The proposed research would therefore bring together two areas of high interest and importance and will contribute to the development of a new generation of drugs, targeting diseases associated with hyperproliferation and abnormal cell size including cancer and heart diseases. Moreover, drugs selectively targeting rRNA synthesis in cells could be used for stimulation of cell growth and proliferation in cell-replacement therapy strategies to the benefit of those with degenerative cell diseases.
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