Question

DNA repair systems are responsible for maintaining genomic fidelity in normal cells despite the high frequency with which mutational events occur. What type of DNA mutation is generated by (a) UV radiation and (b) ionizing radiation? Describe the system responsible for repairing each of these types of mutations in mammalian cells. Postulate why a loss of function in one or more DNA repair systems typifies many cancers.

Answer 1

(a)The most common photochemical product in DNA is a cyclobutane pyrimidine dimer. This product forms when two adjacent pyrimidines (thymines, TT, or cytosines, CC) become linked covalently by their C=C double bonds. These four carbons form a cyclic ring (cyclobutane) that links the two pyrimidines, thus creating a chemical intermediate that is not normally found in DNA. This photochemical product causes a structural kink in the DNA that prevents the pyrimidines from base pairing, and prevents DNA replication. (b)When cells are exposed to ionizing radiation, radiochemical damage can occur either by direct action or indirect action. Direct action occurs when alpha particles, beta particles or x-rays create ions which physically break one or both of the sugar phosphate backbones or break the base pairs of the DNA. A mutation is a change in the nucleotide sequence of a short region of a genome. Many mutations are point mutations that replace one nucleotide with another; others involve insertion or deletion of one or a few nucleotides. Mutations result either from errors in DNA replication or from the damaging effects of mutagens, such as chemicals and radiation, which react with DNA and change the structures of individual nucleotides. All cells possess DNA repair enzymes that attempt to minimize the number of mutations that occur . These enzymes work in two ways. Some are pre-replicative and search the DNA for nucleotides with unusual structures, these being replaced before replication occurs; others are post-replicative and check newly synthesized DNA for errors, correcting any errors that they find.