September 19, 2006 | David F. Coppedge

Genetic Toolkit Manages Dangerous Tools with Safety Switch and Lockbox

Laymen appreciate scientists who can express complex concepts in everyday terms.  Here’s a good example from the Wistar Institute:

Around the home, regularly used tools are generally kept close at hand: a can opener in a kitchen drawer, a broom in the hall closet.  Less frequently used tools are more likely to be stored in less accessible locations, out of immediate reach, perhaps in the basement or garage.  And hazardous tools might even be kept under lock and key.
    Similarly, the human genome has developed a set of sophisticated mechanisms for keeping selected genes readily available for use while other genes are kept securely stored away for long periods of time, sometimes forever.  Candidate genes for such long-term storage include those required only for early development and proliferation, potentially dangerous genes that could well trigger cancers and other disorders should they be reactivated later in life.

The article discusses how researchers at Wistar Institute found a two-molecule complex that governs how the chromatin that packages DNA will become either loosely organized or tightly condensed.  Some unknown switching mechanism determines how ASF1 will bind to one of two similar molecules, HIRA and CAF1, that determine the degree of tight packing:

An unanticipated observation from the study centers on the region of association between the two molecules in the complex.  The researchers knew that one of the two molecules in the complex, called ASF1, associated with a particular molecular partner, HIRA, when directing assembly of the more condensed form of chromatin.  But it could also associate with a different partner, called CAF1, to shepherd assembly of the less condensed form of chromatin.
    On closer study, the scientists discovered that HIRA and CAF1 have nearly identical structural motifs in the regions of interaction with ASF1.  This means that ASF1 can bind to one or the other molecular partner, but not to both.  In other words, the interaction is mutually exclusive: A kind of decision is made by ASF1 as to whether to guide the assembly process towards the more or less condensed forms of chromatin.  What determines the choice?  The relevant factors are unknown for now.

However it works, it’s important: one researcher explained, “Appropriate packaging of the DNA in the cell nucleus is crucial for proper functioning of the cell and suppression of disease states, such as cancer.”  The research has been published online in Nature Structural and Molecular Biology.1


1Tang et al., “Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly,” Nature Structural and Molecular Biology, Oct. 2006, published online: 17 September 2006; doi:10.1038/nsmb1147.

Good work, by scientists operating on design principles (whether they realize it or not).  There was no mention of evolution in the press release.  It would would seem, also, that evolutionary theory would be useless in tracking down the factors that determine which binding takes place.
    You might not have realized that your genetic toolkit has power tools that are dangerous.  Just like you would lock up hunting rifles in a secure cabinet, so that they won’t be used for the wrong purpose, your genetic system has controlled procedures for locking up its dangerous equipment.  Most of the trillions of cells in your body get it right for decades, and even when there’s an accident, the body has other procedures for containing the damage.  It is mind-boggling that all this goes on without our conscious knowledge, so that we can be conscious, and gain knowledge.

(Visited 7 times, 1 visits today)
Categories: Amazing Facts, Genetics

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.