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Scientists Probe the Search and Rescue System in the Cell

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A double-stranded DNA break in a cell is a crisis that can lead to cancer. Fortunately, "an intricate DNA repair system exists which is impressively error-proof and efficient." But this DNA damage repair system has to work fast. Interesting research at Delft University in the Netherlands has provided new insights into how cells solve this "staggering problem," akin to finding a needle in a haystack, "within minutes and with great efficiency."

The Delft team deftly handled DNA molecules and a protein called RecA, using a new instrument that combines magnetic tweezers with laser trapping, enabling the scientists to capture individual molecules and measure the forces that bind them together. This enabled the team to probe beyond what has already been known:

First, proteins form a filamentous structure on the broken DNA end. Second, this filament examines recently copied DNA or the second DNA chromosome (remember that we have two copies of each chromosome) in search of a DNA sequence that matches that of the broken end. Note that this is a daunting task: given that, for example, our human genome contains three billion base pairs, finding your few hundred base pairs of interest, is really like finding a needle in a haystack.
It's been a "mystery for decades" how cells can search for the right sequence to repair a broken DNA strand. Here's what the Delft team found about how RecA is able to recognize the target sequence on the other chromosome that becomes a template for the repair operation:
"In bacteria, the so-called RecA protein is responsible for conducting the search operation. In E. coli bacteria, a filament of RecA protein formed on DNA, searches and pairs a sequence within a second DNA molecule with remarkable speed and fidelity. To do so, individual molecules of RecA first come together to form a filamentous structure on the broken DNA. The filament then grabs DNA molecules in its vicinity and compares their sequence to the sequence of the broken DNA. When a sequence match is found, both molecules bind tightly to one another allowing repair to ensue," says [researcher Iwijn] De Vlaminck (since recently at Stanford University).

"We found that the filament's secondary DNA-binding site interacts with a single strand of the incoming double-stranded DNA during homology sampling. Recognition is achieved upon binding of both strands of the incoming DNA to each of two DNA-binding sites in the filament."

This rapid search and rescue operation allows "wrong" matches to be quickly dissociated, while correct matches bind more tightly: "These are the two elements that lead to the impressive speed and high efficiency of the DNA repair process."

The story might be described this way: scientists intelligently designed instruments to probe a feature of cells that bears the hallmarks of intelligent design: efficient, high-fidelity search and repair. Darwin? They had no need of that hypothesis.

Image credit: Wikipedia.