DNA Repair Helps Prevent Cancer
TEHRAN (Tasnim) – Findings of a new research helped scientists understand how the human body recognizes damaged DNA and how it can prevent cancer.
The biological information that makes us unique is encoded in our DNA. DNA damage is a natural biological occurrence that happens every time cells divide and multiply. External factors such as overexposure to sunlight can also damage DNA. Understanding how the human body recognizes damaged DNA and initiates repair fascinates Michael Feig, professor of biochemistry and molecular biology at Michigan State University.
Feig studies the proteins MutS and MSH2-MSH6, which recognize defective DNA and initiate DNA repair. Natural DNA repair occurs when proteins like MutS (the primary protein responsible for recognizing a variety of DNA mismatches) scan the DNA, identify a defect, and recruit other enzymes to carry out the actual repair.
"The key here is to understand how these defects are recognized," Feig explained. "DNA damage occurs frequently and if you couldn't repair your DNA, then you won't live for very long." This is because damaged DNA, if left unrepaired, can compromise cells and lead to diseases such as cancer.
DNA chains are made of four precise chemical base pairs with distinct compositions. In a paper published in the Journal of Physical Chemistry B (April 26, 2013), Feig and his research team showed that the identification and initiation of repair depended on how the MutS protein bound with the base mismatches.
"We believe that DNA bending facilitates the initial recognition of the mismatched base for repair," Feig said. "Normal DNA is like a stiff piece of rubber, relatively straight. It becomes possible to bend the DNA in places where there are defects."
The biological repair machinery seems to take advantage of this propensity by 'testing' DNA to determine whether it can be bent easily. If that is the case, the protein has found a mismatch and repair is initiated.
"When the MutS protein is deficient in certain people, they have a high propensity to develop certain types of cancer," Feig said. "We're interested in understanding, first of all, how exactly this protein works. The long-term idea is to develop strategies for compensating for this protein, basically substituting some other mechanism for recognizing defective DNA and enabling repair."
The strongest link between diseases and defects from the MutS protein has been made for a specific type of genetically inherited colon cancer.
"If an essential protein like MutS is missing or less than adequate, then the cells will not behave in a normal way," he explained. "They will turn cancerous. The cells will refuse to die and proliferate in an uncontrollable state."
In these cases, cancer is not a result of damaged DNA, but occurs because of a problem in the DNA repair mechanism itself.
Research in this area, being very fundamental in nature, throws up many challenges, but its potential in future impact, Feig believes, is tremendous.
"There are many proteins with different and important biological functions," he said. "Understanding their functions and roles in the human body will be a driving force for research in the near future."