Camilo Ruiz Mejíalll Semester

Medical StudentUPB

• The damage in the DNA is one of the main causes of many pathologies such as cancer and xeroderma pigmentosum, it is for this reason, that Molecular Biology, and other fields of Medicine, have focused on the study of the mechanisms of reparation that the DNA has, such as:

1. Nucleotide excision.2. Nitrougenous basis

excision.3. Recombination repair.4. Repair of mismatches

• The RNA polymerase that it´s attached to the faulty DNA strand, can be pulled backwards by an enzyme in E. Colli, named Uvrd (the human analog it´s called XPB).

• Scienteifics from Ney York University, have found that this interaction, may benefit the excision reparation of the DNA.

• The recoil of the RNA polymerase, exposes damaged DNA, that was covered by the enzyme; this movement makes more accesible the faulty section of the strand to the excision repair enzymes.

• The team from NYU, with some help from a Russian team, used biochemical and genetic experiments, to prove that UvrD, it´s somehow linked to RNA polymerase, and that this interaction, is essential in DNA reparation.

• They also pointed that a elongation factor NusA works and cooperates with UvrD.

• The authors, believed that if this mechanisms could be done in a more smooth process, then, there would be less aging, cancer, and many other pathologies.

• The study also proposed that the main role of the RNA polymerase is not the transcription of the DNA, because it would be a waste of energy to carry out such a complex and long process to synthesize such a small molecule (RNA), they think that the major role of RNA polymerase it´s to protect the DNA from any kind of damage.

• I belive that the RNA polymerase plays an essential role in the preservation of the structure of the DNA molecule, and that we must study this enzyme more, because it could lead to a better understanding of DNA damage, and maybe it would help us find new ways to repair it.

• DNA can be damaged by a number of factors, such as radiation, carbonized material, ultraviolet sunlight among others.

• The cell performs a series of complicated processes to repair the damages on the DNA molecule, this processes involves a repair protein, called ATM.

• A defective ATM, leads to higher risk of cancer.

• A protein called TCTP (Translationally controlled tumor protein), regulates the function of ATM, a KAIST research team found the mechanism of this regulation, proving that TCTP can cambine with ATM and increases it´s catalytic activity.

• In the study, the research team used a widely used organism in Molecular Biology and genetics around the world, called, Drosophilia melanogaster, to prove the role of ATM and TCTP on the reparation process of the DNA.

• The study concluded, that ATM, plays a major role in the reparation on portions of the DNA that have been damaged by radiation, they proved that when the gene expressions of TCTP and ATM are low, an eye exposed to radiation would develop large defects.

• Radiation is one of the major problems that right now our planet faces, and reducing the radiation levels in our atmosphere it´s almost imposible, so we need to focus on how we are going to protect our genetic material from this type of energy, the first step, i think, is to identify the mutations that might happen to our genome that may affect our repair mechanisms against radiation (for example ATM protein).

• If we could find a way to interact with the XPB protein, and making it more effective, as well as interact with RNA polymerase and understand it´s role in DNA reparation, we could reduce the levels of mutation and damage to the DNA, accordingly we could reduce the incidence level of diseases like for example cancer.

• Thats why i think, we should study the RNA polymerase with more attention, because we might be missing something in the role that this enzyme plays in the reparation of the DNA.

• As doctors we cannot make a major change in how our world manages the current radiation levels, what we can do is study mechanisms to reapir the damage that this rays make to our genetic material, for example, using genetic therapy to increase the expression of the gene that encodes the ATM protein to improve the reparation process of damages caused by radiation.

That´s not the only application that this study has, another thing that can be done, it´s finding ways to diagnose a mutation on the gene that encodes either ATM o TCTP protein, to be able work on the risk. that people might have, to develop a series of diseases.

• New York University´s Langone Medical Center. (2014, January 9). Enzyme reverses transcription machinery to aid DNA repair. Genetic Engineering & Biotechnology news (GEN). Retrieved January 24, 2014 from http://www.genengnews.com/gen-news-highlights/enzyme-reverses-stalled-transcription-machinery-to-aid-dna-repair/81249345/

• KAIST Department of Biological Science´s. (2014, January 7). Mechanism of damaged DNA mutation identified. MedicalXpress. Retrieves January 24, 2014 from http://medicalxpress.com/news/2014-01-mechanism-dna-mutation.html