New findings mark step forward in treatment of cancer, genetic disease
Researchers at the Churchill and Tyler labs at the University of Colorado Denver have made an important stride in the future treatment of cancer and genetic disease. Their findings will be published in the Nov. 3 edition of Cell.
Mair Churchill, PhD, and Jessica Tyler, PhD, have developed a three-dimensional
model of two of the protein building blocks of our chromosomes bound to another
protein called Anti-Silencing Function 1 (Asf1). Asf1 helps to make the DNA
within our chromosomes accessible for gene regulation, genetic inheritance,
and the repair of DNA damage. DNA, the molecule which encodes our genetic material, is tightly wound around histone proteins in the chromosomes. Asf1 makes this genetic material accessible by removing these proteins. The researchers discovered the precise way in which Asf1 binds to the histone proteins H3 and H4.
“ This work provides the first molecular insight into how our cells gain access to DNA,” said Tyler, who has been studying the function of Asf1 for nearly ten years. “Cancer and genetic disease occur when genes which should be active become inactive. Because Asf1 helps to activate these genes, it may be a key to the treatment of these diseases.”
Asf1 cannot be seen by even the most advanced microscopes, and so the Tyler lab worked together with Churchill to determine the shape of the protein by a method called X-ray crystallography. “This method uses proteins that have been crystallized and X-rays to decipher their detailed atomic structure,” said Churchill. “It gives a picture of where the atoms are in the proteins, and with that information we make interpretations about the function of the proteins.”
“Understanding the shape of this protein complex helps us better understand its function and behavior,” said Tyler. “In doing so, we may learn to control this behavior and correct the chromosomal defects which cause cancer and genetic diseases, such as fragile X and cystic fibrosis.”
