人体DNA如何自我修复

The biological information that makes us unique is encoded in our DNA¹. 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 initiates³ repair fascinates Michael Feig, professor of biochemistry and molecular⁴ biology at Michigan State University. Feig studies the proteins MutS and MSH2-MSH6, which recognize defective⁵ DNA and initiate² 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 enzymes⁶ 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.

 

Feig, who has used national supercomputing resources since he was a graduate student in 1998, applied⁸ large-scale computer simulations to gain a detailed⁹ understanding of the cellular¹⁰ recognition process. Numerical simulations provide a very detailed view down to the atomistic level of how MutS and MSH2-MSH6 scan DNA and identify which DNA needs to be repaired. Because the systems are complex, the research requires large amounts of computer resources, on the order of tens of millions of CPU core hours over many years.

 

"We need high-level atomic resolution simulations to get insights into the answers we are searching for and we cannot run them on ordinary desktops," Feig said. "These are expensive calculations for which we need hundreds of CPUs to work simultaneously¹¹ and the Texas Advanced Computing⁷ Center (TACC) resources made that possible."

 

As a user of the National Science Foundation's Extreme Science and Engineering Discovery Environment (XSEDE), Feig tasked TACC's Ranger¹² and Stampede supercomputers to accelerate his research. Ranger served the national open science community for five years and was replaced by Stampede (the sixth most powerful supercomputer in the world) in January 2013.

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