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Loosen up, DNA: Leukemia gene changes genetic packaging

ery that turns genes on or off, and only some genes are active in any given cell at any one time.

How our body regulates access to our genes and makes stretches of DNA available is a booming area of study for scientists who study "chromatin remodeling." When a gene is spooled up tightly, it's as if it has been confined by a straightjacket ?it's unavailable or "silenced" and can't be turned on. To become available, a gene must be part of a stretch of DNA that relaxes and loosens up, becoming accessible to a variety of molecular signals.

JAK/STAT signaling is one of the first molecular mechanisms to be identified as controlling chromatin remodeling. Its work resembles that of a criminal mastermind busting a hoodlum out of jail so he can make more mischief. Behind bars, effectively inactive and silenced, the hoodlum ?in this case, a cancer-causing gene causing cells to grow out of control ?is not dangerous. When JAK/STAT frees the scofflaw, it's free to then meet up with its molecular buddies and wreak havoc on the body.

It was just last year that a team of scientists in Germany showed in an article in Nature that tightly wound DNA that is unavailable, known as heterochromatin, can suppress tumor growth by keeping genes that tell cells to grow turned off. Li's paper goes one step further, identifying JAK/STAT, a known cancer-causing pathway in people, as one mechanism that has the ability to turn on sets of genes that have been silenced in this way.

Scientists have thought that JAK/STAT works by directly turning on genes that make tumor cells grow, fitting a more traditional view of how genes are turned on and off. The new findings make the molecule something of a super-oncogene with more global control than scientists had considered. The signaling system thus seems unique because it can both cause cancer directly, or knock out genetic mechanisms that suppress cancer.

"A molecule that is both an oncogene and that also antag
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Source:University of Rochester Medical Center


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