Chemistry Reference
In-Depth Information
Cytosine can stay in its imine form for quite a long period of time, in spite of
the fact that this structure is energetically less advantageous compared to that of
the amine form. The restoration process includes the time needed for the formation
of a cyclic unidirectional structure of water molecules. Thus, when a wrong G-C pair
opening takes place, the less hydrated cytosine needs to pass through the potential
barrier in order to rebuild the surrounding water in a unidirectional cyclic structure.
The time span depends on the number of water molecules participating in the cycle
and in many cases exceeds the time needed for the closing of the helix. In the process
of winding/unwinding of the double helix in the presence of transition metal ions,
one may envisage the following alterations:
M
n+
M
n+
G
*
(3)
M
n+
M
n+
C
*
(4)
G
*
(2)
G
G
(1)
C
C
*
C
*
C
For the second and third examples, the defect that remains after closing of the
disrupted pair is easily recognized by the repair system
in vivo
.
In particular, one should notice that Cu
2+
ions can easily be reduced to the Cu
+
state (UV irradiation, g irradiation, ascorbic acid etc.)
28,31
and the Cu
+
- DNA lifetime
will increase by about 11 orders of magnitude, reaching 10
4
10
5
s .
17
In this case,
Cu
2+
, which is essential for life for many mammals, can be transferred into extremely
toxic soft Cu
+
ions.
Depurination is the second process inducing point defects. Interaction of H
+
with pyridine-type nitrogen atoms, and the preference of transition metal ions to
bind to G-N7 may lead to the hydrolysis of the C-N3 glycosidic linkage, which is
the weakest covalent bond in DNA with a torsion rotation barrier in the range
0.003- 0.006 kcal mol
− 1
74,82
At the moment of base pair opening, the ions will initiate
rupture of the bond and if it is not restored
in vivo
, severe damage of the double
helix called
deletion
will take place. Even if the repair system restores the deleted
base, this may not completely prevent damage, because interaction of metal ions
with the DNA duplex may also lead to DPT (see above), and after depurination of
guanine, cytosine adopts a rare tautomeric imine form. In this case, adenine instead
of guanine will be inserted in the base pair.
−
5
×
2.4 Conclusions
(i)
A thermodynamic model of metal ion interactions with DNA can be used to
establish direct proportional correlation between dynamics and stability con-
stants. This approach is based on the physical model of gas and vapour adsorp-
tion on the surface of solids. Thus, the principal concept of molecular biophysics
regarding biomolecular
structure - dynamics - function
can be reformulated as
structure - stability - function
. One may notice that such an approach highly sim-
plifi es and widens the time intervals (from 10
− 10
s to 10
5
- 10
6
s and more) under
investigation for dynamic characteristics of macromolecules.
