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Researchers reveal structure of protein that repairs damage to cancer cells
Date:4/23/2008

d DNA. They failed because this family of proteins binds DNA weakly, which foils the application of traditional crystallographic methods, He said. His team reinforced the complex by cross-linking the DNA to the protein.

Previous crystal structures of this protein included only a very short, single-stranded segment of DNA, and did not reveal all of its interactions with larger, more biologically relevant strands of DNA.

The technique that they used to grow these crystals is very clever, said Rice, who served as the teams crystallographer. Its a nice application of chemistry to solving important questions in biology.

Knowing which pieces of the enzyme are important for interacting with double-stranded DNA and which pieces are missing when it would prefer a single strand will help us to predict the functions of related proteins, Rice said.

Said He: Were now applying this same strategy to all kinds of other protein-DNA complexes.

The AlkB and ABH2 proteins repair alkylation damage to DNA, including the damage caused by alkylating cancer treatments. Alkylation is the addition of certain chemical groups to DNA and is particularly harmful to rapidly growing cells such as cancerous ones.

In an unexpected development last year, a team of European researchers published studies that identified an obesity gene in humans that belongs to the same family of proteins as AlkB. A defect in this gene, FTO, is associated with a weight gain of nearly seven pounds.

Its surprising and exciting to see that the demethylation function is linked to obesity, He said. Methylation is a type of alkylation that is used to regulate gene expression. One of his future goals is to determine the function of the FTO protein.

Among their many functions, proteins control chemical reactions in the cell by turning genes off and on. This family of proteins might use demethylation as a signal to regulate gene activation, he said. But this
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Contact: Steve Koppes
s-koppes@uchicago.edu
773-702-8366
University of Chicago
Source:Eurekalert  

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