The researchers used both genetic and biochemical methods to dissect actin's role in the INO80 complex. The INO80 complex normally functions in the nucleus to rearrange chromatin the intertwined proteins and DNA that are packaged into chromosomes regulating the expression of many different genes.
The authors found that a mutant form of actin impairs the ability of INO80 to function correctly, implicating actin in the process of chromatin remodeling an exploding field of research with applications in cancer diagnosis and treatment.
In the cytoplasm, actin functions primarily as a polymer. Cytoplasmic actin is a component of the cytoskeleton and the muscle contractile machinery, and is essential for cell mobility, including cancer metastasis. Actin inside the INO80 complex is arranged in a clever way such that it cannot polymerize; instead, actin's monomeric form appears to interact with chromatin.
"Our study challenges the dogma that actin functions through polymerization, revealing a novel and likely a fundamental mechanism for monomeric nuclear actin," Shen said.
New findings for an ancient complex
Because actin and several of the other INO80 components are so highly conserved, even in human cells, this mechanism likely represents an ancient, fundamental role of actin, which has been preserved through evolution.
Shen's group is now teasing out the exact mechanism by which nuclear actin interacts with chromatin. They also hope to extend the results to human cells and to identify potential ways by which nuclear actin could be involved in cancer.
Chromatin is critical for maintaining the delicate balance between gene activation and repression, Shen said. "Disrupting this regulation can lead to cancer, and it remains to be seen whether nuclear actin has a
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center