25 January 2013

XPD Protein Discovered To Scan For Damaged DNA

The XPD scanner (green)is in close contact with a damaged point (red) on the DNA double helix. The damaged DNA strand lies in a deep pocket of the protein to enable a ferrous sensor (Fe) to come into contact with the damaged point, thereby halting the protein as it moves along the DNA.
Image: UZH
Xeroderma pigmentosum group D (XPD) protein, a protein associated with repairing DNA has been discovered to also scan for damaged DNA.

Deoxyribonucleic acid (DNA) is a molecule that contains genetic code or instructions used for the development and function of living organisms. DNA encodes its genetic information through the sequence of four nucleotides (guanine(G), adenine(A), thymine(T), and cytosine(C)).

Whenever DNA is damaged through ultra-violet light, cigarette smoke, toxic fumes, toxins, X-rays and radiation, and metabolic processes, it is repaired by proteins and enzymes such as Superoxide dismutases and methyl guanine methyl transferase (MGMT). Roles of these proteins and enzymes vary from recognizing damage, to correcting the damaged portions or remove them.

Unrecognized damage which does not get repaired, accelerates aging and causes cancer and genetic disorders. There are DNA disorders that involve the body having difficulty repairing DNA. Xeroderma pigmentosum (XP) and Trichothiodystrophy (TTD) are two of these disorders.

A team headed by veterinary pharmacologist and toxicologist Hanspeter Nägeli has now discovered that the protein XPD plays a key role in locating damaged DNA.

XPD protein as scanner

Genetic information is stored on approximately three billion base pairs of adenine/thymine or cytosine/guanine in the thread-like DNA double helix. The researchers reveal that the XPD protein works like a scanner that glides along the DNA double helix, scouring the bases for signs of damage. As soon as one of the protein's ferrous sensors encounters damage as it moves along, it is stopped, thereby marking damaged spots in need of repair. Besides patching up DNA, XPD is also involved in cell division and gene expression, thus making it one of the most versatile cell proteins.

Video: Repairing DNA: Our Best Defense Against Cancer

Basis for possible courses of therapy

While repairing the DNA protects healthy body tissue from damage to the genetic material, however, it diminishes the impact of many chemotherapeutic substances against cancer. "Damage recognition using XPD opens up new possibilities to stimulate or suppress DNA repair according to the requirements and target tissue," explains Hanspeter Nägeli. The results could thus aid the development of new cancer treatments.


University of Zurich
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