Nucleic Acids in Chemistry and Biology

8.10 Biological Consequences of DNA Alkylation

DNA damage is unavoidable and can be divided broadly into two categories. Some forms of damage, such
as mismatches, deamination of bases, base-loss and oxidative damage, arise spontaneously. Others, such as
ionizing radiation, UV radiation and chemical agents including ubiquitous alkylating agents (Section 8.5.3)
arise through environmental influences. Many of these changes can result in errors during the steps of the
DNA replication, recombination and repair, and so lead to modification of the structure of genetic material.
Happily, many of these modifications can be removed successfully by DNA repair machinery.83,84

8.10.1 N-Alkylated Bases

7-Alkylguanineis the predominant product of DNA alkylation. However, methylation at this site appears
not to change the base-pairing of G with C and so is an apparently innocuous lesion. Following N-7 alkylation,

Covalent Interactions of Nucleic Acids with Small Molecules and Their Repair 323

O O B

O

O O

P

P

O O

O

P

P

CO 2

HO OH

HO

P

P

1' O HO–

O O B

O

P

P

HO

O

O

P

P

O

P

B

HO–

O O 4' CO^2 heat B

O O B

O

P

P

O

O CHO

O

P

P

O

HO

P

O HO–

O

O

5'

Figure 8.35 Breaks in DNA resulting from hydrogen atom abstraction and peroxide radical formation at C-1
(upper),
C-4
(centre) and C-5
(lower) in deoxynucleotides followed by mild alkaline treatment (0.1M NaOH,
10min, 20°C)