Biology 335 - Molecular Genetics

DNA Structure

 
The previous pages discussing the chemical structure of the nucleic acids should give you a fairly good grasp of DNA and RNA structure.
In this section, I would like to view that structure in a more biological context.

By way of example,
the E. coli genome is a single circular DNA molecule of approximately
five million base pairs

This corresponds to five hundred thousand turns of the helix
and a linear length of about 1.7 mm.

 
(5 x 106 base pairs)
10 bp per turn

 
=
5 x 105 turns of the helix

 

=

=

(5 x 105 turns) x 3.4 nm per turn

17 x 10 5 nm


1.7 mm long (circumference)
& 2 nm wide

 
Thats a pretty long and thin molecule.

What about the human genome -
three billion base pairs of genome sequence,

three hundered million turns of the helix,
one METER long.

 
(3 x 109 base pairs)
10 bp per turn

 
=

3 x 108 turns of the helix

 

=

=

(3 x 108 turns) x 3.4 nm per turn

10 x 10 8 nm

1 METER long
& 2 nm wide

 
Each cell of your body contains 2 meters of DNA -
which must be faithfully replicated and transmitted intact to each daughter on cell division.

During the growth phase of the cell (G1) this 2 meter long string
must also be accessible to the gene expression machinery of the cell.

The packaging of the genome is hierarchical in nature.

Level I - The B-form of the double helix

Level II - The Nucleosome (beads-on-a-string)

 
the nucleosome is a complex of DNA and Histone proteins.

The Histones are a set of small basic proteins
which are highly conserved in 1o structure (aa sequence) in all eukaryotes

There are 4 core Histone proteins: H2A, H2B, H3 & H4.

They are structurally related -
each Histone contains a characteristic 'Histone fold' (see below)
and
an 'unstructured' N-terminus.

 

Histone proteins are notorious for aggregating in solution. in vivo,
they aggregate with defined stochiometry to form the Histone core of the nucleosome -
an octamer complex containing 2 copies of each of the core Histones.

The octamer complex consists of
a central core of two (H3 + H4) dimers
with two (H2A + H2B) dimers located above and below the central core
as shown in the figure below.

 

In addition to the Histone octamer core,
the nucleosome contains approximately 140 bp of DNA
wrapped two times around the octamer core.

DNA enters the nucleosome via interaction with the (H2A + H2B) dimer,
winds twice around the two (H3 + H4) dimers forming the center of the core
and then exits the nucleosome via interaction with the other (H2A + H2B) dimer
as shown in the figure below

 
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Page 2 of Packaging