-Errors (at a rate of 1x10 -9 ) are introduced during DNA replication -DNA in cells is constantly being altered by cellular constituents, including active oxygen species that are by-products of metabolism -Many environmental agents attack and modify DNA Thus maintenance of the genetic information requires constant repair of DNA damage
Types of DNA Damage: -Spontaneous deamination of some C, A, and G bases in DNA -Spontaneous depurination due to cleavage of the glycosyl bond connecting purines to the backbone (the depurinated sites are called abasic or AP [apurinic] sites) -Bases are oxidized by oxygen species -Occasionally, bases are methylated or alkylated -Ultraviolet radiation may covalently link adjacent pyrimidines along one strand of the DNA to form pyrimidine dimers
Mutations -Mutations are inherited changes in the DNA sequence. They can result (i) from replication errors,(ii) from damage to the DNA, or (iii) from errors during repair of damage. Point mutations are the changes of a single base pair. Transitions are mutations in which one purine is substituted for another, or one pyrimidine is substituted for another. Transversions are point mutations in which purine is substituted for pyrimidine, or vice versa. Missense mutations are point mutations that change a single base pair in a codon such that the codon now encodes a different amino acid. Nonsense mutations are point mutations that change a single base pair in a codon to a stop codon that terminates translation. Triplet expansion is a great increase in the number of specific triplet. Triplet expansion causes many diseases, including Huntington’s disease and fragile X disease.