Transcript DNA Structure

1- B DNA
2- Double helix
3- Antiparallel
4- Major groove
5- Minor groove
6- Sugar puckering
7- C2 endo
8- C3 Exo
9- Syn, Anti
--Right handed
10- A DNA, C3 endo position
11- Z DNA
-- Left handed, G and A in syn position
-- G and (A) in C3 endo position
-- Base stacking
--Hydrogen bond
-- Phosphate position
-- Hoogsteen Base pair
-- Triple stranded helix
-- Genome
-- Relaxed form
-- Super coil
-- Histone like proteins
-- Nucleosome
-- Nucleosome core
--Chromatin
-- Linker
-- Sscaffold
-- Solenoid
--Melting point
Hypochromism. (A) Single-stranded DNA absorbs light more effectively than does double-helical DNA. (B) The
absorbance of a DNA solution at a wavelength of 260 nm increases when the double helix is melted into single
strands.
Step
Melting ΔG
-1
/Kcal mol
TA
-0.12
T G or C A
-0.78
CG
-1.44
A G or C T
-1.29
A A or T T
-1.04
AT
-1.27
G A or T C
-1.66
C C or G G
-1.97
A C or G T
-2.04
GC
-2.70
Structural Parameter
A-DNA
B-DNA
Z-DNA
Direction of helix
rotation
Right handed
Right handed
Left handed
Residue per helical
turn
11
10
12
Pitch (length) of the
helix
28.2 Å
34 Å
44.4 Å
Base pair tilt
20°
-1°
7°
Rotation per residue
32.7°
34.3°
-30°
Diameter of helix
23 Å
20 Å
18 Å
Configuration dA, dT,
dC
anti
anti
anti
of glycosidic bond dG
anti
anti
syn
Sugar Pucker dA, dT,
dC
C3' endo
C2' endo
C2' endo
dG
C3' endo
C2' endo
C3' endo
Topology of major
groove
Narrow, deep
Wide, deep
Flat
Topology of minor
groove
Broad, shallow
Narrow, shallow
Narrow, deep
Major- and Minor-Groove Sides. Because the two glycosidic bonds are not diametrically opposite each other,
each base pair has a larger side that defines the major groove and a smaller side that defines the minor groove.
The grooves are lined by potential hydrogen-bond donors (blue) and acceptors (red).
Propeller Twist. The bases of a DNA base pair are often not precisely coplanar.
They are twisted with respect to each other, like the blades of a propeller.
Axial View of DNA. Base pairs are stacked nearly one on top of another in the double
helix
Step
Stacking ΔG
-1
/kcal mol
TA
-0.19
T G or C A
-0.55
CG
-0.91
A G or C T
-1.06
A A or T T
-1.11
AT
-1.34
G A or T C
-1.43
C C or G G
-1.44
A C or G T
-1.81
GC
-2.17
Histonea Molecular
weight
Number of amino
acids
Percentage Lysine +
Arginine
H1
22,500
244
30.8
H2A
13,960
129
20.2
H2B
13,774
125
22.4
H3
15,273
135
22.9
H4
11,236
102
24.5
a
Data are for rabbit (H1) and bovine histones.
Structure of Histone Acetyltransferase.
The amino-terminal tail of histone H3
extends into a pocket in which a lysine side chain can accept an acetyl group from acetyl
CoA bound in an adjacent site
Histone modifications
Histone proteins can undergo various types of modification, the best studied of these
being histone acetylation.
– the attachment of acetyl groups to lysine amino acids in the N-terminal regions of
each of the core molecules. These N termini form tails that protrude from the
nucleosome core octamer and their acetylation reduces the affinity of the histones for
DNA and possibly also reduces the interaction between individual nucleosomes that
leads to formation of the 30 nm chromatin fiber
Histone acetyltransferases (HATs) – the enzymes that add acetyl groups to histones.
Histone acetylation plays a prominent role in regulating genome expression.
The tails of the core histones also have attachment sites for methyl and phosphate
groups and for the common (‘ubiquitous') protein called ubiquitin.
Ubiquitination of histone H2B is part of the general role that ubiquitin plays in control of
the cell cycle.
Phosphorylation of histone H3 and of the linker histone has been associated with
formation of metaphase chromosomes
Methylation of a pair of lysine amino acids at the fourth and ninth positions from the Nterminus of histone H3.
Methylation of lysine-9 forms a binding site for the HP1 protein which induces
chromatin packaging and silences gene expression
Methylation of lysine-4 has the opposite effect and promotes an open chromatin
structure
Lysine-4 methylation is closely correlated with acetylation of histone H3
Two types of modification may work hand in hand to activate regions of chromatin.
Remodeling is induced by an energy-dependent process that weakens the contact
between the nucleosome and the DNA with which it is associated. Three distinct types of
change can occur
Remodeling, in the strict sense, involves a change in the structure of the nucleosome,
but no change in its position.
Sliding, or cis-displacement, physically moves the nucleosome along the DNA
Transfer, or trans-displacement, results in the nucleosome being transferred to a
second DNA molecule
the proteins responsible for nucleosome remodeling work together in large complexes.
One of these is Swi/Snf, made up of at least 11 proteins, which is present in many
eukaryotes
Direct methylation of DNA also has a silencing effect
Silencing can be implemented is by removing acetyl groups from histone tails
This is the role of the histone deacetylases (HDACs).
HDACs are contained in multiprotein complexes. One of these is the mammalian
Sin3 complex, which comprises at least seven proteins, including HDAC1 and
HDAC2 along with others that do not have deacetylase activity but which provide
ancillary functions essential to the process
Both Sin3 and NuRD contain proteins that bind to methylated DNA.