Cell Nucleus Biogenesis, Structure and Function
417
chromosomes one inherited from each
of the two parents. Humans have 46
chromosomes with about 6
×
10
9
bp DNA
in total. The structure of DNA, with its
acid sugar-phosphate backbone, demands
that some mechanism must have evolved
to
neutralize
the
negatively
charged
phosphate groups in order to fold DNA
so that it might Ft inside a mammalian
nucleus. Note that this amount of DNA
would cover about 2 m if extended, yet
must fold to occupy a nucleus that is
only
10
µ
m in diameter. A family of
small (about 10 kDa) arginine and lysine-
rich proteins called
histones
are responsible
for DNA packaging. The fundamental
structural unit of DNA packaging is called
the
nucleosome
. The core structure of
a nucleosome (±ig. 9) contains
146 bp
DNA wrapped as 1.75 turns over the
surface of a histone octamer. The protein
core
structure
contains
two
sets
of
the four core histones – called
histones
H2A, H2B, H3 and H4 – arranged with
mirror symmetry around the dyad axis
of the nucleosome. The histone genes
themselves are extremely highly conserved
throughout eukaryotes as their proteins
must interact in a very precise way to form
the nucleosome core. The core structure is
in turn deFned by the architecture of the
individual histone proteins (±ig. 9) while
Fig. 9
The nucleosome. High-resolution X-ray crystal analysis can be used to
demonstratethestructureofanucleosome.In this nucleosome core particle, 146 bp of
DNA (turquoise and brown) wraps
1.75 times around the histone octamer. The octamer
of each core contains two molecules each of histones H2A (yellow), H2B (red), H3 (blue)
and H4 (green). Each of the core histones has a central domain with three
α
-helical
regions separated by short coils. Interactions between these domains within the core
determine the core structure. The N-terminal domains are unstructured and can extend to
the outside surface of the nucleosome. The dimensions of this core structure are
10
×
6 nm. (Reproduced from Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F.,
Richmond, T.J. (1997) Crystal structure of the nucleosome core particle at 2.8 angstrom
resolution,
Nature
389
, 251–260. With permission of Palgrave-Macmillan Publishing.)
(See color plate p. xxxi).
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