March 27, 2011 | David F. Coppedge

Your DNA Repairman Is Handy as an Octopus

Some 10 times a day in a given cell, your DNA breaks on both strands.  This is an emergency.  Unless repaired quickly, serious diseases, like cancer, can develop.  But no fear: the first responder is an octopus-shaped protein complex that rushes to the rescue, wraps around the damaged site, and brings in all the parts needed to fix it.  Such mechanical acrobatics in the cell are only now coming into clearer focus.
    A press release at the Scripps Research Institute described this amazing repair system called MRN with its three protein subunits (Mre11-Rad50-Nbs1; for illustration, see Science Daily).  The researchers wanted to find out how MRN “can repair DNA in a number of different, and tricky, ways that seem impossible for ‘standard issue’ proteins to do,” the press release said.  These proteins are not static balls of amino acids; they have dynamic, interactive, moving parts.  The motor in the complex, Rad50, “is a surprisingly flexible protein that can change shape and even rotate depending on the task at hand.”  Here’s the octopus part of the story:

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. 

They saw “a lot of big movement” in the repair operation.  First, the complex has to assess the damage:

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.  “The same complex has to decide the extent of damage and be able to do multiple things,” [John] Tainer [Scripps Research Professor] said.  “The mystery was how it can do it all.

Tainer described how some of the parts interact: “Rad50 is like a rope that can pull.  It appears to be a dynamic system of communicating with other molecules,” he said.  It uses ATP, the energy currency of all life, to get into 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 in order to repair it.
    How a set of proteins can sense damage, migrate to a repair site, assess the extent of the break and select the correct repair option, link up to other tools, bring in parts, and put everything back together again is surely one of the wonders of biology coming to light with new observing techniques.  The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Energy, and published in Nature Structural and Molecular Biology,1 March 27, 2011.
    The abstract did not mention evolution except to say that the parts are “conserved” (unevolved) across all living things.  The researchers studied this complex in yeast and archaea – among the simplest of microbes.  A different paper in a different journal studied another wonder of the cell without mentioning evolution (except to mention “evolutionarily conserved proteins”).  In PLoS Biology,2 Linton Traub [U of Pittsburgh] discussed how proteins coat vesicles that dive into the cell membrane to bring in substances from outside the cell.
    In “Regarding the Amazing Choreography of Clathrin Coats,” Traub described clathrin-mediated endocytosis (see 10/17/2003, 05/15/2005, 11/04/2005, 02/02/2010, bullet 3).  He started with a recounting of the discovery of clathrin, a three-spoke protein that wraps around vesicles like a geodesic dome, and then described some of the latest findings: “Yet, what we have learned over the past decade is that the assembly of these core components is augmented and precisely regulated at vesicle bud sites by an abundance of additional proteins” – at least 40, at last count.  The realization that so many players are involved in this critical import process “puts to rest the parsimonious assertion that the complexity of clathrin coat assembly is wildly overstated,” he said.


1.  Williams…Tainer et al, “ABC ATPase signature helices in Rad50 link nucleotide state to Mre11 interface for DNA repair,” Nature Structural and Molecular Biology, (published online 27 March 2011), doi:10.1038/nsmb.2038.
2.  Linton M. Traub, “Regarding the Amazing Choreography of Clathrin Coats,” Public Library of Science: Biology (PLoS Biol) 9(3): e1001037. doi:10.1371/journal.pbio.1001037>

The facts themselves scream intelligent design so clearly, any additional comments would be superfluous.  Was evolution useful to any of this research?  Does an octopus need a hot air balloon?

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