Alejandro Cardona Echandia

Molecular Biology, Faculty of Medicine

2015

Replication of the Genetic Material in Eukaryotes and Prokaryotes

EJERCICIOS

Introduction

• The replication of the genetic material is process that is conceptually simple but molecularly complicated, from which a DNA mother molecule is synthesized in a new one, creating two DNA daughters molecules, with identical sequence of the original.

• Occurs in coordination with the cell division, in the S phase of the Cell Cycle.

For the REPLICATION,

the cell will need…

• DNA Polymerase• DNA ligase. • Topoisomerase.• Helicases, primases. • RNAsa H.• Okazaki fragments. • Single Stand DNA Binding Protein.

ABSENCE OF TUMOR-SUPRESSING GENE DERILS DNA REPLICATION,

LEAVING CELLS VULNERABLE TO CANCER

Cell duplication and growth is essential to sustaining life, and in order for this critical function to take place, cells must unwind the tight ball of DNA in their nucleus and then duplicate their genomic information.

This is a delicate maneuver, ripe for errors or omissions, and if PTEN, a known tumor-suppressor gene, has mutated or is absent, the replication process derails and can lead to cancer development.

“PTEN enzyme structure”

Date: July 7. Source: Weill Cornell Medical College

PTEN is a tumor suppressor . It acts as a dual specificity protein phosphatase: •Dephosphorylates phosphorylated proteins on tyrosine , serine and threonine residues •Lipid-phosphatase:

•Uses Mg as a Cofactor.

It is critical for tumor suppressor function.

In the late-1990s, scientists discovered the PTEN gene and growing evidence has shown that PTEN is a powerful tumor suppressor. Less clear, however, was whether and how PTEN works when it comes to DNA replication — and if loss of PTEN could impact this central process of genome transmission to allow development and progression of cancer.

"Tumors without PTEN are more sensitive to chemotherapies that work by targeting DNA replication, while normal cells or cancers with active PTEN resist these treatments," said Dr. Wen H. Shen.

Each year about 14 million people

globally are told they have cancer and 8 million die from the disease

Each year about 14 million people

globally are told they have cancer and 8 million die from the disease

Dr. Wen H. Shen

“Our study shows that PTEN acts as a guardian of this process by sitting right on the replication fork to recruit other essential protective partners," she said. "Without PTEN, this protection machinery falls apart. DNA is then unprotected, which leads to fork stalling and failure to restart."

PTEN function is absent in a wide variety of cancers — for example, 70 percent of prostate cancers have PTEN mutation or deletion. Because of this, researchers are currently testing PTEN to see if it's a marker of aggressive cancer and for personalized cancer treatment.

"Patients whose cancers have lost PTEN or harbor mutations in the gene are known to have poorer outcomes than patients with active PTEN," Dr. Shen said. "Our expectation is that a PTEN blood test in the near future will help clinicians decide on the right therapies for each cancer patient, and in particular, to benefit this subgroup of cancer patients carrying PTEN mutations."

Personal Opinion

I think that the future of the actual Medicine is going to be focused in part of the molecular biology and biochemistry, because each more time, new diseases are emerging with problems in micro-molecular structures, so its time to consider it as a very important part of science and try to intensify more in them.

Otherwise, for me it’s very important to continue investigation about this enzyme, because, pitifully, cancer in killing thousands of people every year, and we are face to face with a possible solution for this disease.

BACTERIA USE DNA REPLICATION TO TIME KEY

DECISION

In spore-forming bacteria, chromosomal locations of genes can couple the DNA replication cycle to critical, once-in-a-lifetime decisions about whether to reproduce or form spores. Like most microorganisms, Bacillus subtilis bacteria are single-celled creatures with one goal: to reproduce by making copies of themselves.

Date: July 9. Source: Rice University.

But survival isn't always that simple. For example, when food gets scarce, B. subtilis must decide between two possible paths: shut down, form a dormant spore ("sporulation") and wait for better times or split into two cells and gamble that there is enough food for at least one more generation.

But that decision is one of the most important for the bacteria. because "If the organism waits too long, it can starve before it finishes transforming into a spore. If it acts too early and forms a spore too soon, it can be overwhelmed and out-reproduced by competitors." said Oleg Igoshin .

"Successful sporulation requires two complete copies of the bacterial chromosome, so coordination between the sporulation decision and the completion of DNA replication is very important," Narula said.

B. subtilis is harmless to humans, but some dangerous bacteria like Bacillus anthracis, the organism that causes anthrax, also form spores by a similar mechanism.

B. Anthracis B. Subtilis

"A good analogy might be a semester-long course in biology. Lessons are presented in a particular order, and students are tested after they learn. If the final exam were given in the first week, students would almost certainly fail."

To divide and reproduce, bacteria must make a duplicate copy of their DNA. Because replication of circular bacterial DNA always initiates at one particular point, Narula surmised that the location of the KinA (green) and Spo0F (purple) genes could be crucial. If one were located near the point where DNA replication began, the cell would contain two copies of that gene -- doubling the rate of production of that protein -- throughout the DNA replication period. If the other gene were located on the part of the circle that was copied last, the ratio of KinA to Spo0F would be one-to-one only when DNA replication was nearly completed.

"We found that the relative location of sporulation genes on the DNA circle were similar in more than 30 species of spore-forming bacteria, including Bacillus anthracis," Igoshin said

Personal Opinion

I think that we should pay attention on the conclusion that the Dr. Igoshin said at the final of his article, because it could be very useful at the time that we are going to attack some on the pathologies that we find actually. How he said, the variability of the bacteria's depends of the place that the DNA replication starts, so, in the future, we can find inhibitors for the majority of those DNA fragments and counteract much of pathogens that we could find, making treatment even better and more effective.

IMPORTANCE AND UTILITY OF DNA REPLICATION FOR

MEDICINE AREA First of all, we have to recognize

de importance of the DNA replication for life, not only for human survival also for the other kingdoms that need it. Because, if our DNA didn´t get replicated, we wouldn´t have cell division and cycle will be interrupted and the cell would die.

DNA replicates semi-conservative manner, DNA molecules daughters will always be an old and a new chain of nucleotides that contain all the biological information in the body.

This is useful in treating many diseases, thanks to cell cycle become worse in the case of cancer and tumor cells. And precisely this is the target of many drugs and treatments which the patient is provided, in the case of chemotherapy , all with the aim to curb the growth of cells that do so much damage to the body.

But we can not just based on a curative medicine , preventive medicine can be the salvation for many of the diseases that can be prevented or early treatment may prevent these worsened.For example, It has already been shown that the preventive treatment of some diseases such as certain cancers, tumors or accelerated cell growth may be inhibited with certain foods , vitamin supplements or drugs in their default.

Promote research and investigation in medicine basic areas, such as cell biology,

molecular biology, biochemistry and pharmacology, with the aim of expanding

medical knowledge and implement humanity solutions from each area of

knowledge.

REFERENCES

1) Martínez Sánchez, Lina María; Vargas Grisales, Natalia; Mejía Cardona, Laura; Osorio Ospina, Felipe; Ramírez Pulgarín, Sergio. “Biología Molecular”. 8va Edición. Medellín. Colombia. Editorial Universidad Pontificia Bolivariana. Pp: 101 - 108.

2) H. Shen, Wen; Andreopoulou, Eleni; Iadecola, Costantino; Stefan Worgall, Anne Moore. “Absence of Tumor-Suppressing Gene Derails DNA Replication, Leaving Cells Vulnerable to Cancer”. Weill Cornell. July 7 2015. http://weill.cornell.edu/news/news/2015/07/absence-of-tumor-suppressing-gene-derails-dna-replication-leaving-cells-vulnerable-to-cancer.html.

3) Narula, Jatin; Kuchina, Anna; D. Lee, Dong-Yeon; Fujita, Masaya; M. Süel, Gürol; Oleg A. Igoshin. "Bacteria use DNA replication to time key decision: Bacterial decision circuit makes use of circular chromosome." ScienceDaily. ScienceDaily, 9 July 2015. <www.sciencedaily.com/releases/2015/07/150709162428.htm>.

4) Images retrieved from www.google.com.

In each medical act must be present respect for the patient plus ethical and moral concepts; then consciousness and science are always on the same side, the side of humanity.

(René Gerónimo Favaloro)