(based on So, S., et al. "Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites." Journal of Cell Biology, early release - published December 21, 2009, 10.1083/jcb.200906064)
We're all familiar with ATMs - automated teller machines - giving us our hard-earned money and accepting checks and deposits. But deep inside all of our cells, a different kind of ATM is called upon to save DNA, the currency of life. This ATM - ataxia telangiectasia mutated (try saying that three times fast!) - is a protein that is one of the first responders when DNA becomes damaged by radiation. Like an ambulance, it speeds to the accident site and helps the injured DNA. Although scientists have a good idea of how ATM responds, there has been debate over one specific part of ATM's role in repairing DNA. However, recent research from scientists at the University of Texas sheds new light on the functions of this molecular ambulance.
But first thing's first -- just how does ATM respond? ATM, like all proteins in the body, has specific jobs to do. Of course, proteins don't run around inside a cell working all the time; that would cause chaos. Proteins, like people, do their work when it's needed, and rest the remainder of the time. But in order to do work, proteins like ATM must first be activated, or switched on, by a process called phosphorylation. Once ATM is activated, it migrates to the DNA damage site, and then switches on other proteins by the same phosphorylation process, triggering a cascade of DNA repair events.
However, the activation of ATM is complex. Like a room with multiple light switches, ATM can be activated in different places and at different times. One of the most common switches is a specific place on the protein called S1981. Though scientists know that S1981 is phosphorylated in response to DNA damage, there has been contradictory evidence about whether this is actually necessary for ATM's repair activities.
To examine this problem, researchers from the University of Texas tagged ATM with a fluorescent label, essentially making the protein glow, and easy to see with a fluorescence microscope. The research group discovered that both "normal" ATM and mutated ATM - with a mutation at the S1981 site - migrated to damaged DNA without a problem. However, they found that the mutated ATM had much more trouble "holding on": after 2 hours, only 20% of the altered ATM was found around the damaged DNA whereas 65% of normal ATM was present in the area. From this, the researchers were able to establish that S1981 is specifically required for sustained localization of ATM to damaged DNA.
Next, they examined whether S1981-mutated ATM was able to switch on other proteins that it needed to activate in order to trigger DNA repair. The group found that two specific proteins which are dependent on ATM activation, and which also congregate with ATM at the DNA damage site, fail to be phosphorylated by the mutant ATM. However, a third protein target of ATM, which is not the vicinity, is phosphorylated equally well by either the normal or mutant ATM proteins. This led the researchers to an interesting conclusion: S1981 is responsible for ATM's ability to switch on other proteins at the DNA damage site, but not elsewhere.
As a result of this research, the exact functions of ATM are more well-known than they were before. Although an investigation into one specific part of a protein may not seem like a groundbreaking discovery, ATM's role in sensing DNA damage, and triggering DNA repair, to stop the spread of mutations is vitally important in maintaining all of our cells. Indeed, people with mutated ATM proteins have an increased risk of cancer and immune system deficiencies. This research also illustrates, at a wider level, just how complex proteins are. Compared with this ATM, invented by nature, a simple man-made automated teller machine pales by comparison.
This ATM isn't for dispensing money -- it's for repairing DNA
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