Most chemotherapy drugs are designed to block DNA replication; majority of the generally and successfully drugs are DNA-damaging agents. The DNA targeting has proven to result in comparatively potent and discerning distribution of cancerous cells. Compounds which are empirically identified with anticancer activity have been indicated to target DNA as the crow flies or through enzyme inhibition which controls the integrity of the DNA of offers the DNA building blocks. With the revelation of the DNA structure various therapeutic modlaities have been established namely; the antimetabolites which, depletes the nucleotides comprising folic acid, an example being methotrexate. Alkylation agents also impose a direct damage to the DNA; for example nitrogen mustard and derivatives. Intercalators have also been advanced, such as actinomycins that bind the DNA inhibiting the utilization as a substrate by other enzymes. The most successfully and widely used anticancer agents are general DNA damaging chemicals comprising of topoisomerases inhibitors, alkylating agents, antimetabolites and DNA covalent modification causing agents. As these agents were advanced, it became distinct that the vital entity which drove tumorigenesis was the DNA. That is, the DNA is broken in cancerous cells and its lifecyle is varied in cancerous cells as compared to normal cells, and cancerous cells are more probable to attain DNA damage because of the high rate of DNA replication (Snyder, 2007). Therefore, the alteration of the DNA within cells is a widely-preferred targeted therapy for cancer.
There are four basic differences in the regulation of gene expression in prokaryotic and eukaryotic systems. First, eukaryotes require sophisticated controls over the gene expression. Although there are fundamental similarities the transcription of genes amongst prokaryotes and eukaryotes; for example, the polymerase in the RNA binds the gene’s upstreamon its enhancer to begin the transcription process, multicellular eukaryoted control the differentiation of cells through precide and complex spatial and temporal gene expression regulation. Secondly there is a variation in the mode of transcription control; prokaryotes do not have a nucleus, thus the transcription and its control is a simple process while eukaryotes have to transcribe through a sequence of processes; mRNA processing, transfer of the matured mRNA to the cytoplasm. Third there is a difference in the gene clustering; prokaryotes have operons where genes of similar roles are grouped together. On the other hand eukaryotes do not have any operans. Ever gene has an enhancer and promoter element. The fourth distinction is the ground state of DNA expression, with prokaryotes, the RNA polymerase can access any promoter in the DNA sequence with the absence of repressors or activators; non-restrictive. In the contrary, eukaryotes have a restrictive ground state of DA expression. Although there exist strong promoters, they are not active until the recruitment to the promoter is accomplished by the transcription factors (Struhl, 1999).
References
Snyder R.D. (2007). Assessment of atypical DNA intercalating agents in biological and in silico systems. Mutat Res. 623, 1–2, 72–82.
Struhl, K. (1999). Fundamentally different logic of gene regulation in eukaryotes and prokaryotes. Cell, 98, 1–4
