New Powerful DNA Repair Single Protein Complex Discovered


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Normal but dangerous strand breaks occur with the DNA double helix about 10 times a day in every cell due to ultraviolet light and radiation damage, etc.  This creates an emergency.  If these breaks are not quickly repaired, serious chromosomal rearrangements can occur that lead to cancer.  The first responder to rush to the rescue  looks like an octopus, and wraps around the accident scene to perform the repairs.  These mechanical technicians in the cell are now beginning to be understood after 10 years of research.

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Energy. A press release at the Scripps Research Institute states:

“In a paper published in an Advance Online Edition of Nature Structural and Molecular Biology March 27, 2011, the scientists say that the complex’s motor molecule, known as Rad50, is a surprisingly flexible protein that can change shape and even rotate depending on the task at hand.”

The research paper stated that the components of this super protein structure are “conserved,” which means unevolved.  The report continues:

“The finding solves the long-standing mystery of how a single protein complex known as MRN (Mre11-Rad50-Nbs1) can repair DNA in a number of different, and tricky, ways that seem impossible for “standard issue” proteins to do, say team leaders Scripps Research Professor John Tainer, Ph.D., and Scripps Research Professor Paul Russell, Ph.D., who also collaborated with members of the Lawrence Berkeley National Laboratory on the study.”

The report further reads:

“The scientists say that the parts of the complex, when imagined together as a whole unit, resemble an octopus: the head consists of the repair machinery (the Rad50 motor and the Mre11 protein, which is an enzyme that can break bonds between nucleic acids) and the octopus arms are made up of Nbs1 which can grab the molecules needed to help the machinery mend the strands.”

When rescue workers initially arrive at an emergency scene, the first thing they must do is identify and assess the injuries.  The report explains the general idea of the process:

“When MRN senses a break, it activates an alarm telling the cell to shut down division until repairs are made. Then, it binds to ATP (an energy source) and repairs DNA in three different ways, depending on whether two ends of strands need to be joined together or if DNA sequences need to be replicated.”

Tainer explains: “The same complex has to decide the extent of damage and be able to do multiple things.  The mystery was how it can do it all.”

In this study, Tainer and Russell were able to produce crystal and X-ray scattering images of parts of where Rad50 and Mre11 touched each other.  The four (4) images of what these proteins look like when the complex is bound to ATP and when it is not are displayed above.

The four images demonstrate how ATP binding allows Rad50 to drastically change its shape. When not bound to ATP, Rad50 is flexible and floppy, but bound to ATP, Rad50 snaps into a ring that presumably closes around DNA as if it were an octopus in order to repair it.

The research also reveals a busy transport system that Trainer refers to as “big movement on a molecular scale” involved with the repair operation.  He added, “Rad50 is like a rope that can pull. It appears to be a dynamic system of communicating with other molecules.”

Aside from the complex cellular machinery involved in this process, the functions being performed are also quite sophisticated.  This set of proteins has the ability to sense damage, then be transported substantial distances to the accident site to initiate repairs.  The damage must be assessed, a choice must be made as to the correct procedure to restore the damage, and the proper materials must be retrieved to perform the repair work.

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