DNA Mutations

Methylated/Oxidated

Base modification on C8 of purines

Alkylated

Base modification on heterocyclic N

Loss of NH2 —> carbonyl

Base modification on amine of adenine and cytosine

Broken, leads to base loss

Base modification of glycosidic bonds

Tautomers

Molecular states that are in equilibrium

Stability

Associated with base tautomerization

Imino

Amino tautomer

Lactim

Lactam tautomer

Incorrect base pairing and mutations

Tautomers can lead to…

Deamination

Conversion of cytosine into uracil

Deamination frequency

500/day/cell

DNA uracil glycosylase

Fixes deamination

Transition mutations

Results from tautomerization and deamination

B-Glycosidic bond hydrolysis

Mutation that results from nitrogenous base loss

B-Glycosidic bond hydrolysis frequency

200,000/day/cell

Abasic sites

Result in strand breakage

Deaminating Agents

Other chemicals in DNA stability (nitrites, NO2-)

Oxidizing agents

Other chemicals in DNA stability (superoxide, hydroxyl (radical))

Transversion mutation

Transition and transversion mutations

Regulation

Function of “good” alkylating agents

“Good” alkylating agent

Methylation of cytosine silencing genes

Good alkylating agent epigenetics

Carcinogen

Function of “bad” alkylating agents

“Bad” alkylating agent

O⁶ Methylguanine

Causes G-C —> A-T mutations

N⁷ Methylation

Leads to B-Glycosidic bond hydrolysis and strand breaks

UV light

causes thiamine dimers