Fixing DNA damage

The Nobel Prize in chemistry 2015 was awarded to Tomas Lindahl of Sweden, Paul L Modrich of the USA and Aziz Sancar (Turkish-American) for their works that led to a detailed understanding of the DNA damage and how cells repair the damaged DNA, providing new inroads into fighting cancer. This revelation would help drive a revolution in the chemical treatment of cancer by developing new drugs that target molecular paths used by tumour cells to proliferate. Thousands of alterations occur to a cell’s genome every day through spontaneous changes induced by ambient radiation, free radicals and carcinogenic substances. Despite all these environmental pressures, the DNA, by and large remains intact. Basic studies of how a living cell functions uncovered a range of molecular systems monitoring and repairing the damaged DNA and protecting the genetic material from disruption. Various processes were elucidated by the trio and proved important for cancer prevention and treatment. Thus, the DNA repair plays a vital role in human health.

Understanding DNA repair
The work of Tomas Lindahl over the years paved the way for better understanding and treatment of cancer. We live in a world where we constantly undergo environmental exposures to radiation damage and other carcinogenic agents. As a result, it is difficult to avoid damages to the DNA. Tomas showed that DNA is an inherently unstable molecule subject to decay even in psychological situations. He identified a new group of DNA enzymes and elucidated their role in repairing damaged DNA.

Paul L Modrich’s work gave a detailed biochemical understanding of the processes, initially in bacterial, and later in animal cells.

Aziz Sancar carried out mechanistic studies of DNA repair, mapping how cells repair the DNA, and prevent the damaging errors from appearing and proliferating in the genetic information. One or more of these repair systems are damaged in many types of cancer. Aziz transformed the field of DNA repair from genetics to a detailed molecular description of the mechanisms underlying the repair and showed how cells safeguard genetic information after repairing the damage. This is a constant phenomenon in the human body as our DNA is continuously being damaged and thousands of spontaneous changes occur to a cell’s genome.

Defects occur when a DNA is copied during cell division. A host of molecular mechanisms continuously monitor and repair the DNA to prevent disruption of genetic material and save our body from complete chemical chaos. The DNA repair involves a variety of mechanisms that help ensure that the genetic sequence (as expressed in the DNA) is maintained and the errors due to the damage are not allowed to accumulate. The repair also involves action of enzymes, which detect the damage to the DNA and effect its repair.

At least on Earth, DNA, the double helix molecule, seems to be the universal blueprint for biological life, right from the most ancient archaebacteria. The same genetic basis (with transfer and messenger RNA) has existed for at least three billion years, underlying all creatures ranging from the minute Diplococcus (barely visible to the microscope) to the gigantic Diplodocus (one of the largest dinosaurs). The genetic information of the DNA is contained in the sequence of bases along the molecule. The manufacture of proteins in a cell takes place in ribosome. The information for determining the correct sequence of amino acids in the protein is carried to the ribosome by the messenger RNA and amino acids are brought to their correct position (in the protein) by the transfer RNA. It may be recalled that the Nobel Prize in chemistry 2009 was shared by the Indian chemist Venkataraman Ramakrishnan (along with Ada Yonath and Thomas Steitz) for elucidating the structure of the ribosome.

In developing countries there are sharp increases in environment-induced cancers owing to proliferation and use of carcinogenic substances and atmospheric pollutants. The researches that won Nobel Prize for elucidating DNA repair could help reduce such cancerous diseases. Any changes in the code (due to the DNA damage) result in the insertion of incorrect amino acids in protein chains. A typical gene therapy for cancer involves introducing tumour suppressing genes into the cancer cells to prevent uncontrollable cell division. Some therapies introduce genes that direct production of substances, like Interleukin-2, to stimulate the immune system and destroy tumour cells. Gene therapies are already underway for many cancer types.
 
Pioneering medical discovery
The Nobel Prize in medicine 2015 has been awarded to three scientists for their pioneering work in curbing parasitic diseases like malaria and roundworm infections. Half of the prize was awarded to Youyou Tu of China for her work on artemisinin, a drug based on ancient Chinese tribal herb known as sweet wormwood or Artemisia annua. A Mao-era project to look for a cure for malaria within the traditional Chinese medicine helped Youyou’s discovery. For two millennia, Chinese healers were using leaves from the sweet wormwood plant to cure different types of fevers.

Combing through thousands of chemicals for new combination therapies and sifting through literature of traditional Chinese medicine led to this herb, called qinghao in Chinese, which was used in folk remedies as early as 168 B C.

Youyou’s team collected 2,000 recipes from over 600 herbs. The project resulted in the discovery of antimalarial drug, artemisinin, which is one of the most successful transformations of traditional therapy into modern medicine. In a couple of years, hundreds of scientists have tested thousands of synthetic compounds without any success. Thus the attention was turned to China’s traditional medicine.

The other half of the prize was awarded to Satoshi ŌOmura of Japan and Irish born William C Campbell for a new class of drugs with extraordinary efficiency against parasitic diseases. Drugs derived from avermecin have radically lowered incidences of elephantiasis, filariasis and river blindness caused by parasitic worms. Avermecin is derived from soil-dwelling bacteria. Satoshi, a microbiologist, isolated a new strain of bacteria group called Streptomices and successfully cultured it in the lab. William discovered that a component of one of Satoshi’s cultures was active against parasites. This became avermecin. This discovery reminds us of the culture of Penicillin which won the Nobel Prize in medicine 1945.