Organizarea structurala

a ADN-ului uman

3 109 base pairs - the human

genome
DNA, RNA and polypeptides are
large polymers defined by a linear
sequence of simple repeating units
linear backbone of alternating sugar
and phosphate residues
sugar in DNA molecules is deoxyribose,
a 5 carbon sugar, and successive sugar
residues are linked by covalent
phosphodiester bonds

 Covalently attached to carbon atom

number 1 (one prime) of each sugar
residue is a nitrogenous base
Four types of base are found:
adenine (A), cytosine (C), guanine
(G) and thymine (T) and they consist
of heterocyclic rings of carbon and
nitrogen atoms

 divided into two classes: purines (A and G) have

two joined heterocyclic rings; pyrimidines (C
and T) have a single such ring
A sugar with an attached base is called a
nucleoside.
A nucleoside with a phosphate group attached
at carbon atom 5 or 3 constitutes a nucleotide,
the basic repeat unit of a DNA strand
The composition of RNA molecules is similar to
that of DNA molecules, but differs in that they
contain ribose sugar residues in place of
deoxyribose and uracil (U) instead of thymine

 The linear backbone of a DNA molecule

and of an RNA molecule consists of
alternating sugar residues and phosphate
groups
In each case, the bond linking an
individual sugar residue to the
neighbouring sugar residues is a 3, 5phosphodiester bond. This means that a
phosphate group links carbon atom 3 of a
sugar to carbon atom 5 of the
neighbouring sugar

 The structure of DNA is an

antiparallel double helix
Whereas the RNA molecules within a
cell normally exist as single
molecules, the structure of DNA is a
double helix in which two DNA
molecules (DNA strands) are held
together by weak hydrogen bonds to
form a DNA duplex

 Hydrogen bonding occurs between laterally

opposed bases, base pairs, of the two strands of the
DNA duplex according to Watson-Crick rules:
adenine (A) specifically binds to thymine (T) and
cytosine (C) specifically binds to guanine (G)
As a result, the base composition of DNA from
different cellular sources is not random: the amount
of adenine equals that of thymine, and the amount
of cytosine equals that of guanine
The base composition of DNA can therefore be
specified unambiguously by quoting its %GC (= %G
+ %C) composition. For example, if a source of DNA
is quoted as being 42%GC, the base composition
can be inferred to be: G, 21%; C, 21%; A, 29%; T,
29%

 DNA can adopt different types of helical structure

A-DNA and B-DNA are both right-handed helices
(ones in which the helix spirals in a clockwise
direction as it moves away from the observer)
They have respectively 11 and 10 base pairs per
turn
Z-DNA is a left-handed helix which has 12 base pairs
per turn
Under physiological conditions, most of the DNA in a
bacterial or eukaryotic genome is of the B-DNA form
in which each helical strand has a pitch (the
distance occupied by a single turn of the helix) of
3.4 nm

 As the phosphodiester bonds link carbon atoms

number 3 and number 5 of successive sugar
residues, one end of each DNA strand, the so-called
5 end, will have a terminal sugar residue in which
carbon atom number 5 is not linked to a
neighboring sugar residue
The other end is defined as the 3 end because of a
similar absence of phosphodiester bonding at
carbon atom number 3 of the terminal sugar
residue
The two strands of a DNA duplex are said to be
antiparallel because they always associate
(anneal) in such a way that the 5 3 direction of
one DNA strand is the opposite to that of its partner

 The two strands are antiparallel because they

have opposite directions for linking of 3 carbon
atom to 5 carbon atom
The structure shown is a double-stranded
trinucleotide whose sequence can be
represented as: 5 pCpGpT-OH 3 (DNA strand on
left) / 5 pApCpG-OH 3 (DNA strand on right)
(where p = phosphodiester bond and -OH =
terminal OH group at 3 end)
This is normally abbreviated by deleting the p
and OH symbols and giving the sequence on
one strand only (e.g. the sequence could equally
well be represented as 5 CGT 3 or 5 ACG 3)

 the two strands are wound round

each other to form a plectonemic coil
The pitch of each helix represents
the distance occupied by a single
turn and accommodates 10
nucleotides in B-DNA

 Genetic information is encoded by the linear

sequence of bases in the DNA strands (the primary
structure)
Consequently, two DNA strands of a DNA duplex are
said to have complementary sequences (or to
exhibit base complementarity) and the sequence of
bases of one DNA strand can readily be inferred if
the DNA sequence of its complementary strand is
already known
describe a DNA sequence by writing the sequence of
bases of one strand only, and in the 5 3 direction
This is the direction of synthesis of new DNA
molecules during DNA replication, and also of the
nascent RNA strand produced during transcription

 However, when describing the sequence

of a DNA region encompassing two
neighboring bases (really a dinucleotide)
on one DNA strand, it is usual to insert a
p to denote a connecting phosphodiester
bond [e.g. CpG means that a cytidine is
covalently linked to a neighboring
guanosine on the same DNA strand, while
a CG base pair means a cytosine on one
DNA strand is hydrogen-bonded to a
guanine on the complementary strand

The genetic code is

degenerate
The genetic code is a three-letter code
There are four possible bases to choose from at each
of the three base positions in a codon
There are, therefore, 64 (=43) possible codons
but only 20 different amino acids are specified
As a result, the genetic code is said to be
degenerate:
each amino acid is specified on average by about
three different codons
Certain amino acids (such as methionine or
tryptophan, in the case of the nuclear genetic code)
are specified by only a single codon; others,
including leucine and serine, are specified by six
codons

 The most fundamental unit of packaging is the

nucleosome
This consists of a central core of eight histone
proteins, small highly conserved basic proteins of
102135 amino acids
Each core comprises two molecules each of histones
H2A, H2B, H3 and H4, around which a stretch of 146
bp of double-stranded DNA is coiled in 1.75 turns
Adjacent nucleosomes are connected by a short
length of spacer DNA. Electron micrographs of
suitable preparations show a string of beads
appearance. The string of beads, approximately 10
nm in diameter, is in turn coiled into a
chromatin fiber of 30 nm diameter.

The interphase chromosome seems to consist of these

chromatin fibers, probably organized into long loops as described
below.
During cell division, the chromosomes become ever more highly
condensed.
The DNA in a metaphase chromosome is compacted to about 1/10
000 of its stretched-out length.
Loops of the 30 nm chromatin fiber, containing 20100 kb of DNA
per loop, are attached to a central scaffold . This consists of
nonhistone acidic proteins, notably topoisomerase II
an enzyme which has the interesting ability to pass one DNA
double helix through another by cutting a gap and repairing it
Topoisomerase II and some other chromatin proteins are known to
bind to AT-rich sequences, and the chromatin loops may be
attached by stretches of several hundred base pairs of highly ATrich (>65%) DNA (scaffold attachment regions)
In the chromatids of a metaphase chromosome the loop-scaffold
complex is compacted yet further by coiling

 The estimated packaging ratios (the

degree of compaction of the linear
DNA duplex) for human
chromosomes are 1:6 for
nucleosomes, 1:36 for the 30 nm
fiber and >1 :10 000 for the
metaphase chromosome.