Cells have a variety of processes for repairing damage to DNA. First, the damage must be of a form that can be detected by a repair mechanism. Deletion of one or more base pairs results in a chemically correct DNA molecule and cannot be fixed by enzymes. However, removal of one base from a pair, replacement of one base with a noncomplementary base, or other chemical changes to the nucleotides produce recognizable distortions in the DNA molecule.
TABLE 6.3 Partial List of Human Genetic Disorders
Cri-du-chat syndrome (partial deletion of chromosome 5) Down syndrome (triplication of chromosome 21)
Klinefelter syndrome (XXY sex chromosome constitution; 47 chromosomes) Turner syndrome (X0 sex chromosome constitution; 45 chromosomes)
Dominant mutations Chondrodystrophy Hepatic porphyria Huntington's chorea Retinoblastoma
Recessive mutations Albinism Cystic fibrosis Diabetes mellitus Fanconi syndrome Hemophilia
Xeroderma pigmentosum Source: Based on Williams and Burson (1985).
For example, a particular type of damage caused by UV radiation is the formation of covalent bonds between the pyrimidine residues of two adjacent thymidine bases. (Normally, the bases are joined only through the sugar-phosphate groups.) This thymine dimer produces strain in the DNA molecule. The bonds can be removed by a special enzyme called photoreactivation enzyme. Interestingly, this enzyme requires a photon of blue light to complete the repair. It is present in humans as well as prokaryotes.
Another type of repair involves several enzymes. Excision repair uses a variety of enzymes that "patrol" the DNA molecule, remove bases that they recognize as damage, and patch the molecule using DNA polymerase. Any damage that distorts the double helix structure can stimulate this mechanism.
Some humans have an inherited autosomal recessive condition called xeroderma pigmentosum. These persons are exceedingly sensitive to getting skin cancer from exposure to sunlight. The condition can be diagnosed in infancy, enabling people to lead fairly normal lives by protecting themselves from exposure to the sun. The condition seems to be related to a number of different mutations, including about seven that affect excision repair, and to reduced activity of the enzyme that uses blue light to repair thymidine dimers.
A third repair mechanism, called recombinational repair, comes into play when damage is missed by the other mechanisms, but comes to interfere with the replication process.
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