DNA Repair & Genetic Mutations

Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Chromosomal mutations occur when an abnormal number of chromosomes is inherited. Point mutations occur when a nucleotide is swapped for another nucleotide and can be missense, nonsense, or silent mutations. Frameshift mutations occur when a nucleotide is added or deleted, and expansion mutations occur when a given trinucleotide sequence is repeated along the chromosome. Genetic mutations are the basis for most inherited diseases. Common disorders caused by DNA mutations include sickle cell disease, Huntington disease, and Tay-Sachs disease.

Although DNA fidelity is highly protected, DNA can still be damaged by a number of environmental factors, reactive oxygen species, and errors in DNA replication. DNA repair is a continuous process in which the cell corrects the damage. The cell has multiple mechanisms it can use to repair DNA. During replication, the cell has proofreading machinery within the DNA polymerase itself. For single-stranded DNA damage, the cell can use excision repair techniques and photorepair. For double-stranded DNA breaks, the cell can use homologous recombination or nonhomologous end joining. When normal DNA repair processes fail owing to age, dysfunction, or an overloaded system, unrepaired DNA damage can lead to apoptosis, cellular senescence, or malignant tumors.