DNA repair helps 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.

Results from computer simulations show that it is energetically less expensive to bend mismatch-containing, defective DNA (G:T, C:C, C:T, G:A, G:G, T:T, A:A, A+:C) vs. non-defective DNA (containing A:T or G:C base pairs). DNA repair mechanisms likely take advantage of this feature to detect defective DNA based on an increased bending propensity. Credit: Michigan State University

The key here is to understand how these defects are recognized. "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.Understanding how the human body recognizes damaged DNA and initiates repair fascinated Michael Feig, professor of biochemistry and molecular biology at Michigan State University. Feig studied 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.

A high-level atomic resolution simulations was needed. "These are expensive calculations for which we need hundreds of CPUs to work simultaneously and the Texas Advanced Computing Center (TACC) resources made that possible."

DNA chains are made of four precise chemical base pairs with distinct compositions.The research is being carried out by, Feig and his research team showed that the identification and initiation of repair depended on how the MutS protein bound with the base mismatches.

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," . research i being carried out, 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,". "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.