[ RadSafe ] Article: Code Beyond Genetics in DNA --- Implications on radiation exposures?

[John Jacobus]

>From the NYT, at
http://www.nytimes.com/2006/07/25/science/25dna.html?_r=1&th&emc=th&oref=slogin

Another example of why biology is more complex than we
can imagine
 
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July 25, 2006

Scientists Say They’ve Found a Code Beyond Genetics in
DNA 

By NICHOLAS WADE
Researchers believe they have found a second code in
DNA in addition to the genetic code. 

The genetic code specifies all the proteins that a
cell makes. The second code, superimposed on the
first, sets the placement of the nucleosomes,
miniature protein spools around which the DNA is
looped. The spools both protect and control access to
the DNA itself.

The discovery, if confirmed, could open new insights
into the higher order control of the genes, like the
critical but still mysterious process by which each
type of human cell is allowed to activate the genes it
needs but cannot access the genes used by other types
of cell.

The new code is described in the current issue of
Nature by Eran Segal of the Weizmann Institute in
Israel and Jonathan Widom of Northwestern University
in Illinois and their colleagues.

There are about 30 million nucleosomes in each human
cell. So many are needed because the DNA strand wraps
around each one only 1.65 times, in a twist containing
147 of its units, and the DNA molecule in a single
chromosome can be up to 225 million units in length. 

Biologists have suspected for years that some
positions on the DNA, notably those where it bends
most easily, might be more favorable for nucleosomes
than others, but no overall pattern was apparent. Drs.
Segal and Widom analyzed the sequence at some 200
sites in the yeast genome where nucleosomes are known
to bind, and discovered that there is indeed a hidden
pattern.

Knowing the pattern, they were able to predict the
placement of about 50 percent of the nucleosomes in
other organisms.

The pattern is a combination of sequences that makes
it easier for the DNA to bend itself and wrap tightly
around a nucleosome. But the pattern requires only
some of the sequences to be present in each nucleosome
binding site, so it is not obvious. The looseness of
its requirements is presumably the reason it does not
conflict with the genetic code, which also has a
little bit of redundancy or wiggle room built into it.

Having the sequence of units in DNA determine the
placement of nucleosomes would explain a puzzling
feature of transcription factors, the proteins that
activate genes. The transcription factors recognize
short sequences of DNA, about six to eight units in
length, which lie just in front of the gene to be
transcribed. 

But these short sequences occur so often in the DNA
that the transcription factors, it seemed, must often
bind to the wrong ones. Dr. Segal, a computational
biologist, believes that the wrong sites are in fact
inaccessible because they lie in the part of the DNA
wrapped around a nucleosome. The transcription factors
can only see sites in the naked DNA that lies between
two nucleosomes.

The nucleosomes frequently move around, letting the
DNA float free when a gene has to be transcribed.
Given this constant flux, Dr. Segal said he was
surprised they could predict as many as half of the
preferred nucleosome positions. But having broken the
code, “We think that for the first time we have a real
quantitative handle” on exploring how the nucleosomes
and other proteins interact to control the DNA, he
said. 

The other 50 percent of the positions may be
determined by competition between the nucleosomes and
other proteins, Dr. Segal suggested.

Several experts said the new result was plausible
because it generalized the longstanding idea that DNA
is more bendable at certain sequences, which should
therefore favor nucleosome positioning.

“I think it’s really interesting,” said Bradley
Bernstein, a biologist at Massachusetts General
Hospital.

Jerry Workman of the Stowers Institute in Kansas City
said the detection of the nucleosome code was “a
profound insight if true,” because it would explain
many aspects of how the DNA is controlled. 

The nucleosome is made up of proteins known as
histones, which are among the most highly conserved in
evolution, meaning that they change very little from
one species to another. A histone of peas and cows
differs in just 2 of its 102 amino acid units. The
conservation is usually attributed to the precise fit
required between the histones and the DNA wound around
them. But another reason, Dr. Segal suggested, could
be that any change would interfere with the
nucleosomes’ ability to find their assigned positions
on the DNA.

In the genetic code, sets of three DNA units specify
various kinds of amino acid, the units of proteins. A
curious feature of the code is that it is redundant,
meaning that a given amino acid can be defined by any
of several different triplets. Biologists have long
speculated that the redundancy may have been designed
so as to coexist with some other kind of code, and
this, Dr. Segal said, could be the nucleosome code.


+++++++++++++++++++
e to the x, dy dx, e to the x, dx
Tangent, Secant, Cosine, Sine
3.14159
Square Root, Cuberoot, udv
Slipstick, slideroot
NCE

Cheerleaders chant from my old undergraduate college.
-- John
John Jacobus, MS
Certified Health Physicist
e-mail:  crispy_bird at yahoo.com

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