What Is the DNA Damage Response?

October 27, 2015 Brigham and Women's Hospital

Stephen J. Elledge, PhD

Stephen J. Elledge, PhD

Stephen J. Elledge, PhD, is a co-recipient of the 2015 Albert Lasker Basic Medical Research Award for discoveries that have illuminated the DNA damage response. Learn more about DNA damage response and Dr. Elledge’s contributions to this area of study.

Our DNA is under constant threat of damage from a variety of physical and chemical sources. From the natural byproducts created when we digest food to ultraviolet light from the sun, a multitude of factors can react with our DNA and cause chemical changes. Some risk factors for DNA damage – such as smoking cigarettes – can be eliminated, but others cannot.

If left unchecked, chemical changes to DNA can have severe health consequences, leading to cancer and other diseases related to cell growth. If detected, damaged DNA can be repaired by molecular tools within cells that can remove or restore the damaged portion of DNA. The DNA damage response (DDR) refers to the pathway that senses DNA damage and sets in motion the needed steps to repair and protect DNA.

Today, much is known about how the DDR controls DNA repair, and these insights have led to a better understanding of the health consequences when steps in this process go awry. But several decades ago, much of how this process works remained a mystery.

In the 1940s, Evelyn Witkin, PhD, discovered bacteria that were resistant to the damaging effects of UV light. She discovered a critical cell division “checkpoint” that prevents bacterial cells from dividing until their DNA has been repaired.

In the 1980s, Dr. Elledge studied a DNA damage-responsive pathway in more complex organisms, uncovering a signal transduction pathway that sensed changes in DNA and broadcast that information throughout the organism. His discoveries led to an understanding of how human cells maintain stability of their genomes to prevent diseases such as cancer and neurodegeneration.

Today, research teams all over the world, including Dr. Elledge’s lab at Brigham and Women’s Hospital and Harvard Medical School, continue to uncover new components related to the DNA damage response and DNA replication regulatory pathways, and are exploring how these pathways could inform cancer therapies in the future.

Learn more about Dr. Elledge and his research:

– Haley B.

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