Saptaparna Dasgupta, Bennett University
Human exonuclease V (EXO5) is an ATR-regulated nuclease that is specific to the DNA structure. It is also associated with BLM, to mark the start point of the replication fork in a strand of DNA. Research states that an elevated level of EXO5 in tumor cells results in increased mutation within the cells. Which thus, leads to poor rates of survival of patients. It therefore can be concluded that a high level of EXO5 is directly influencing the oncogenic potential in humans.
RADX protein:
The RADX protein attracted the attention of researchers as it can have two biologically alternate effects; with only one mechanism of action. David Cortez, Ph.D. professor and chair of Biochemistry said that it is interesting according to him that a protein could switch biological function, without altering its function. RADX is involved at the site of DNA synthesis, the replication fork. Cortez, Ph.D. Chair for Innovation in Biochemistry along with his colleagues made the RADX invention several years ago. Since that time, RADX was associated with the DNA replication mechanism of cells.
Mechanism of fork reversal:
The invention by Cortez et. al, revealed that RADX also regulates the process of fork reversal. It occurs as a backup mechanism in cases of failure of the DNA replication machinery. In the situation of DNA lesions or any other barrier during replication, the cell responds using the mechanism of fork reversal. Also, the occurrence of some kind of barrier during replication was observed often in every cell division cycle. On the contrary, if there are no barriers or DNA lesions at the time of DNA replication, then in those cases the replication fork does not stop or reverses.
The ‘track’ of RADX:
Recent studies by Madison Adolph and Archana Krishnamoorthy, reveal that RADX has different effects on the replication fork. The effects depend on the conditions of the ‘track’ that the replication mechanism follows. They also reported that RADX protein only in cells having stress (lesion or barrier) promotes fork reversal. On the other hand, in the unstressed cells (cells with no lesions or barriers) RADX prevents the process of fork reversal. Thus, it was inferred that RADX works only when it is required by the cells to function.
RAD51 protein:
The researchers discovered the functioning of RADX and concluded that RADX works by binding with RAD51 protein. RAD51 is required only at controlled levels to cause the fork reversal mechanism. This entire process is referred to as a fundamental process in DNA replication and cell division.
Relation of RADX with cancer:
It was reported by Cortez that if the process of DNA synthesis does not happen correctly, then mutations take place, which further results in cancer and development-related disorders. RADX ensures the DNA synthesis process occurs accurately and gets completed. Recent findings state that RADX plays a role in the cell response to chemotherapy. RADX along with BRCA2 protein race with each other for binding on the site of RAD51. BRCA2 is a protein that is associated with the risk of breast and ovarian cancer. Although the role of RADX towards cancer has been tested successfully in vitro, the in vivo results are yet to be discovered.
Also read: Proteome plasticity at high temperatures!
Reference:
- Hambarde, S., Tsai, C.-L., Pandita, R. K., Bacolla, A., Maitra, A., Charaka, V., Hunt, C. R., Kumar, R., Limbo, O., Le Meur, R., Chazin, W. J., Tsutakawa, S. E., Russell, P., Schlacher, K., Pandita, T. K., & Tainer, J. A. (2021). EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart. Molecular Cell, 81(14), 2989-3006.e9. https://doi.org/10.1016/j.molcel.2021.05.027
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Author info:
Saptaparna Dasgupta, currently a B. Tech 3rd year student, pursuing Biotechnology, is a diligent student and determined in terms of her career goals. Being a budding biotechnologist, she is open to all research fields of her course and passionate about knowledge. She is focused and constantly tries to improve her writing skills, also a project enthusiast and is fond of gaining hands-on experience in laboratories. She believes that all hard works and effort pay off eventually and follows this as the motto of her life.
Well written 💯