"These results support the idea that in higher organisms, the mechanisms of silencing and dynamic gene regulation - once believed to be separate functions governed by separate genes - in fact represent two sides of the same coin," said Parkhurst, a developmental biologist. While Sir2 has been studied extensively in yeast, analogous versions of the gene exist in many higher life forms as well. Human cells, for example, have seven such silencing genes. Because some of the key genetic components of Sir2's gene-silencing pathway in lower organisms are identical to those in humans, scientists can exploit the power of yeast and fruit fly genetics to study complex human processes, from early development to cancer growth.
"It appears that Sir2 in higher organisms, including humans, can get the right gene to shut on or off at the right time. This is crucial for maintaining the integrity and normal functioning of cells," said Parkhurst, also an affiliate associate professor of zoology at the University of Washington College of Arts and Sciences.
Mutations, or defects, in Sir2 result in disastrous effects. In lower organisms, for example, such genetic errors have been associated with a shortened life span.
In the Parkhurst lab, Sir2 mutations have been linked to drastic developmental defects and foiled gender assignment, taking a significant toll on equality of the sexes, at least as far as the fruit fly population is concerned. "We noticed that flies with Sir2 mutations weren't too happy," said Rosenberg, a graduate student in the Parkhurst lab. "There were far too few males in the fly stocks."
"In the absence of Sir2, there's the wrong kind of gene expression for the sex chromosomes present. A female can express as if she's a male, and vice versa. That can lead to all kinds of problems. In flies, it leads to death," Parkhurst said.
In humans, in
'"/>
Contact: Kristen Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center
16-May-2002