A Challenge to Central Dogma

Nandini Pharasi, Jaypee Institute of information technology

Thomas Jefferson provided the first evidence that RNA segment can be written back to DNA which is a great challenge to central dogma. Each cell in our body has a specific mechanism that is it undergoes duplication of DNA to form new cells. The enzyme behind this is polymerase, which synthesizes a long change of polymer of nucleic acid and this further assembles into RNA and DNA molecules. In the case of DNA, the template uses base-pairing interactions, which helps adenine to combine with thymine whereas cytosine pairs with guanine. In the case of RNA, guanine is replaced by another nitrogenous base, uracil. RNA messages build by polymerase enzymes that is like copying notes from the book of DNA master recipes. Hypothetically it was considered that polymerases work only in one direction that is from DNA to DNA or from DNA to RNA.

What is the central dogma of life?

The central dogma is a process that gives us information about the genetic flow or how the information is passed from one generation to the next. It is the main mechanism behind the conversion of DNA to RNA and then from RNA to protein. The cell undergoes replication (DNAàDNA) followed by transcription (DNAà RNA) and then further translation (RNAà proteins). In replication DNA polymerase replicates the DNA which further produces copies of DNA that goes to the next step of transcription with the help of RNA polymerase. In transcription, DNA is converted into RNA and that RNA goes to translation, which is the process by which RNA is converted into proteins with the help of ribosomes. Until recently, this flow was considered to be the only way of transfer of information because it prevents messages from being rewritten back from RNA to DNA.

The challenge to central dogma:

Researches now raise many questions about this widely accepted theory, which poses a huge challenge to central dogma. This finding will help us in the future to open many doors towards other researches which will help to understand the mechanism of conversion of RNA messages to DNA in a better way. RNA messages might be used as templates for rewriting genomic DNA. A team of Dr. Pomerantz’s provided interesting results by scrutinizing polymerase θ – an exceptional polymerase.

Polymerase θ belongs to a family of higher eukaryotes, evolved from an enzyme named Pol1 which gives it a unique property of forming helicase fusion protein. Pol θ represents a promising cancer drug target. This means it is highly expressed in oncogenes that cause cancer. Pol θ is highly error-prone. It can acquire mutation, which is the reason behind the inactive proofreading domain. Polθ repairs DNA but has no control over mutations that might occur during proofreading. The study hypothesized that Polθ has RNA-dependent DNA synthesis activity.

The researchers tested polymerase theta by experimenting on HIV (Human Immunodeficiency Virus) through reverse transcriptase which is possibly the best study for this discovery. This study showed that polymerase theta is capable of converting RNA messages into DNA.

It is better than duplicating DNA to DNA because it shows fewer errors in RNA template, it works more efficiently in reverse transcriptase while using polymerase theta used by RNA template to rewrite DNA. The collaborated group used X-Ray Crystallography to be able to change the shape of RNA into a more bulky structure, which was a triumph unique achievement among all polymerases. Researchers say that the main function of polymerase theta is to act as reverse transcriptase. In healthy cells, these polymerases will be mediated by RNA that helps DNA repair and in abnormal cells such as cancerous cells, this polymerase theta is found to be expressed highly.

Also read: Understanding the importance of forensic odontology

Reference:

1. Chandramouly, G., Zhao, J., McDevitt, S., Rusanov, T., Hoang, T., Borisonnik, N., Treddinick, T., Lopezcolorado, F. W., Kent, T., Siddique, L. A., Mallon, J., Huhn, J., Shoda, Z., Kashkina, E., Brambati, A., Stark, J. M., Chen, X. S., & Pomerantz, R. T. (2021). Polθ reverse transcribes RNA and promotes RNA-templated DNA repair. Science Advances, 7(24), eabf1771. https://doi.org/10.1126/sciadv.abf1771

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