What is DNA synthesis? Its importance in cancer development

DNA synthesis - producing a copy of DNA

The cell is the smallest living structural unit making up the body. The molecule that controls cells, DNA, carries all the genetic information inherited from parents. To constitute this information, DNA contains a system made up of nucleotides. These nucleotides consist of adenine (A), guanine (G), cytosine (C) or thymine (T) bases, a 5-carbon sugar and a phosphate group. Genetic information is formed by arranging nucleotides in different combinations. This genetic information enables the production of one of the molecules required for the body’s vital functions, proteins . Proteins have a wide variety of roles in the body, ranging from DNA synthesis to production of the hormone insulin. When cells divide, genetic information must be preserved . Cell division is a biological process required for growth, wound healing and the production of new blood cells. During this division process, a copy of DNA must be produced and these copies must be transferred to two separate cells. DNA is a helical structure consisting of two strands containing nucleotides. Nucleotides pair with one another as guanine-cytosine and adenine-thymine. The process of producing a copy of DNA is called DNA synthesis . During DNA synthesis, the genetic information of the dividing cell must be copied exactly.

DNA synthesis follows a semiconservative model. In other words, half of the DNA strand is old and the other half contains newly formed DNA.

DNA synthesis begins when various proteins position the helicase enzyme in the region to be synthesized so that it can separate the DNA double strand using ATP. Immediately after helicase is positioned and starts opening the strand, the enzyme DNA polymerase arrives at the opened region. DNA polymerase extends the new DNA strand in a particular direction, using the old DNA strand as a template (in the 5’ >> 3’ direction). Because one of the newly synthesized strands has a synthesis direction of 3’ >> 5’, DNA polymerase cannot synthesize this region. This is because DNA polymerase can synthesize DNA only in the 5’ >> 3’ direction. To overcome this problem, the primase enzyme synthesizes, at regular intervals at the 3’ end, RNA primers. These RNA primers allow the polymerase enzyme to synthesize this strand in the 5’ >> 3’ direction as well. However, following this synthesis, the DNA region between two RNA primers cannot be joined by DNA polymerase. This separate segment is called an Okazaki fragment . Joining this fragment is the responsibility of the ligase enzyme . The compression ahead of the synthesis region caused by the helical structure of DNA is corrected by the enzyme topoisomerase . This process continues from the start of the synthesis region to its end.

Why is understanding DNA synthesis important for cancer?

During DNA synthesis, the DNA polymerase enzyme may not always pair bases correctly. DNA polymerase has an error-correction mechanism. Despite this mechanism, the rate of this error in a normal human cell is one in 10 billion (our bodies are estimated to contain 37 trillion human cells, and of every 300 of these cells, 1 divides each day). Errors in nucleotides are called mutations .

As a result of these mutations, the protein produced from the relevant gene region may change, or its production may be blocked or increased. If this region is a proto-oncogene (encoding a protein that could cause cancer development), a mutation can turn it into an oncogene (active in cancer development). For example, a mutation that increases production of the Myc protein, which is involved in one of the DNA synthesis pathways, can trigger cancer development. Conversely, if a mutation inactivates the retinoblastoma protein, a suppressor of the same pathway, this can also trigger cancer development. Thus, even the slightest error in the seemingly simple process of DNA synthesis can cause cancer through mutations accumulating over a long period. Most chemotherapies used in clinical practice today target DNA synthesis in cancer cells.