Written by Dr. Ambika Tewari Edited by Dr. Mónica Bañez-Coronel
Mutations in the Huntingtin protein impair DNA repair causing significant DNA damage and altered gene expression
Our genome houses the entirety of our genetic material which contains the instructions for making the proteins that are essential for all processes in the body. Each cell within our body, from skin cells that provide a crucial protective barrier, immune cells that protect us from invading species and brain cells that allow us to perceive and communicate with the world contains genetic material. During early development in every mammalian species, there is a massive proliferation of cells that allows the development from a one-cell stage embryo to a functional body containing trillions of cells. For this process to occur efficiently and reliably, the instructions contained in our genetic material need to be precisely transmitted during cell division and its integrity maintained during the cell’s life-span to guarantee its proper functioning.
There are many obstacles that hamper the intricate and highly orchestrated sequence of events during development and aging, causing alterations that can lead to cell dysfunction and disease. Internal and external sources of DNA damage constantly bombard the genome. Examples of external sources include ultraviolet radiation and exposure to chemical agents, while internal sources include cell processes that can arise, for example, from the reactive byproducts of metabolism. Fortunately, nature has evolved a special group of proteins known as DNA damage and repair proteins that act as surveyors to detect erroneous messages. These specialized proteins ensure that damage to the DNA molecules that encode our genetic information is not passed to the new generation of cells during cell division or during the expression of our genes, ultimately protecting our genome. Many genetic disorders are caused by mutations in the genetic material. This leads to a dysfunctional RNA or protein with little or no function (loss of function) or an RNA or protein with an entirely new function (gain of function). Since DNA repair proteins play a crucial role in identifying and targeting mistakes made in the message, it stands to reason that impairment in the DNA repair process might lead to disease. In this study, Rui Gao and colleagues through an extensive collaboration sought to understand the connection between altered DNA repair and Huntington’s disease.