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(for Mn
2+
) to 1 (for Cu
+
).
15
Consequently, metal-induced depurination of the DNA
chain in wrong Watson-Crick pairs depends mainly on the probability of base pair
opening. In conclusion, interactions of H
+
and M
n
+
with N3 and N7 of purines will
increase the probability of prototropic tautomerization of purines and, fi nally lead
to the transition of N9 purines in pyrol-type nitrogens followed by consecutive
depurination.
Later the question of base pair opening was studied directly in DNA under
different conditions using NMR and other methods.
77- 81
The results obtained by
these authors are in agreement with the model proposed by Crothers.
76
2.3.3 Formation of Point Defects
For steric reasons, metal-ion-induced DPT may take place only at G-N7 in GC pairs,
which can be approached by transition metal ions in DNA. DPT may also take place
at G-N3 (GC pair) and T-O2 (AT pair) sites, but in this case only H
+
ions can
approach these sites. Thus, it may be concluded that transition metal ions cause DPT
exclusively in GC pairs via G-N7, while H
+
can do it at both GC and AT via G-N7,
G - N3 and T - O2.
DPT and depurination
in vivo
can lead to the gene mutations i.e. point muta-
tions (transition and deletion, respectively). In the fi rst case, the geometry of the
base pairs that undergo DPT remains the same, or changes very slightly, and it may
stay unnoticed in the processes of replication and correction. Nevertheless, the
hydration of the correct Watson-Crick pairs differs from the wrong ones (trans-
ferred by DPT).
14
We do not know the biological mechanisms of detection of these
differences. In the view of solid-state physics, one of the major characteristics of
these kinds of defect is their formation energy (
U
). In the case of DNA, this energy
lies in the range 0 (for Cu
+
) to 2.4 kcal mol
− 1
(for Mg
2+
) (Table 2.4 ). The values of
the energy (
U
) given in the table were obtained by the Boltzman distribution.
In our case,
P
∆
v
n
700
1
represents the ratio of G-C pairs in keto and
enol tautomeric forms: P
DPT
=
n
ket
/
n
en
−
=
cm
DPT
M
+
e
−
U
/
RT
.
Let us consider the probable mechanism of transition-type mutations in a
G-C pair of DNA by an example involving the interaction of Cu
2+
with G-N7.
Schematically we can describe it as follows:
≈
the helix
unwinding
mutation
A
G
*
C
T
Cu
2+
G
*
G
DPT
C
*
C
A
*
A
C
T
*
- rare tautomeric form of bases
