The stereochemistry of these [22] cyclobutane dimers requires that Py<>Py formation in native
DNA is predominantly an intrastrand process with photoaddition involving adjacent pyrimidines.^67 The
trans-synisomer may perhaps result from regions of Z-DNA, and NMR analysis of an oligomer contain-
ing this lesion has indicated that in this structure it causes a larger distortion of helical structure. The struc-
ture of a duplex DNA dodecamer containing a cis-syn-thymine photodimer d(GCACGAAT<>
TAAG)d(CTTAATTCGTGC) has been determined (Figure 8.31a).^68 It shows that the overall helical axis
bends approximately 30° toward the major groove and unwinds approximately 9°. This structure is con-
sistent with the ability of T<>T drastically to slow DNA synthesis opposite the dimer site, yet still direct-
ing the incorporation of A residues opposite to the dimer during bypass(Section 8.11).
T<>T photodimers revert to monomers on irradiation at wavelengths shorter than 254 nm, while dimers
containing cytosine residues are easily deaminated by mild hydrolysis so that subsequent photoreversion
provides yet another source of the C→T base transition by the following reaction sequence:
Many other types of pyrimidine photoproduct have been isolated from irradiated DNA. The most note-
worthy are the pyrimidine(6-4)pyrimidone photoadductsand the ‘spore photoproduct’. The latter is
formed from a radical generated by loss of a hydrogen atom from the methyl group of thymine (Figure
8.30b) and is the major UV-induced photoproduct in the dehydrated state of DNA found in bacterial
spores. Pyrimidine(6-4)pyrimidone photoproducts are formed by UVC with an incidence of about 25%
that of the cyclobutane photodimers, with T(6-4)C being twice as abundant as T(6-4)T. With UVB, such
(6-4) products undergo isomerization to give a ‘Dewar-benzene’structure that on UVC irradiation reverts
to its precursor (Figure 8.30b).
CT C T U T UT
HO
→<>→hh^ <>→^2 Covalent Interactions of Nucleic Acids with Small Molecules and Their Repair 317
NNHOO
dRMeNNNH 2O
dRNHNOO
dRMeNNHNHO
dRNHNOO
dRMeNNNH 2
OdRNHNOO
dRMeNNOdRNHNOO
dRMeNNOdRNNHOO
dRMeNHNOO
dRNNHOO
dRNHNOO
dRMe MeHH
NNHOO
dRNHNOO
dRMe MeHHhν
254 nm- NH 3
Dewar≥254 nm
≤254 nmspore photoproduct<254 nmhν^ hν >254 nm
hν
sens.hν (–H*)cis-syn T<>T trans-syn T<>T(6-4)photoproducta
NNHOO
pentoseNNHOO
pentoseHOH
NNNH 2O
pentoseNNNH 2O
pentoseHOHNH 3
U Chν, H 2 O
-H 2 Ohν, H 2 O
-H 2 OU*C*NNHNH 2O
pentoseHOHHO
H 2 ObFigure 8.30 Pyrimidine photochemistry. (a) Photohydration of ribo- and deoxyribo-uridine and cytidine with
deamination of cytidine photohydrate leading to uridine. (b) Pyrimidine [22]photodimers and other
photoproducts formed from DNA