The 2015 Albert Lasker Basic Medical Research Award honors two scientists for their discoveries concerning the DNA-damage response, a mechanism that protects the genomes of all living organisms. Evelyn M. Witkin (photo), Ph.D., (Rutgers University), now 94, established its existence and basic features in bacteria, and Stephen J. Elledge, Ph.D., (Brigham and Women's Hospital) uncovered its molecular pathway in more complex organisms. The details of the two systems differ dramatically, yet they share an overarching principle. Both coordinate the activity of a large number of genes whose products shield creatures from potentially lethal harm. Throughout their lives, cells withstand an onslaught of insults to their DNA. External agents such as chemicals and radiation bash it, and it also sustains abuse from within when normal physiological processes blunder. In humans, such events deliver tens of thousands of genetic wounds every day. The DNA-damage response detects not only DNA anomalies, but also other dangers, such as interruptions in the DNA-copying process. Living creatures then implement a multi-pronged strategy to ensure survival. Bacteria, for instance, ramp up their DNA-repair capabilities, halt cell division to provide time to mend damage, and amplify their mutagenic facility. At first glance, the third activity might seem to conflict with the first two, but evolution has covered many bases—boosting the microbe's ability to fix DNA and also increasing variation within the population, thus enhancing adaptability. Like bacteria, mammalian cells construct DNA-repair equipment and arrest division when they detect genetic peril. In addition, when the extent of injury overwhelms DNA-restorative capacities, the DNA-damage response sparks cell suicide.
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