Dna Damage and Repair
Consequences Of Dna Damage
Figure 2 shows some of the consequences of DNA damage. As mentioned above, DNA damage can be induced by external or internal sources. Ultraviolet (UV) irradiation and ionizing irradiation are examples of exogenous sources of stress. Reactive oxygen species generated by the oxidative phosphorylation that occurs in mitochondria, and thus via cellular metabolism, is an example of an endogenous type of stress. Mutations in DNA can occur via replication of the damaged DNA whereby they become "fixed." Lesion bypass or replication errors can give rise to other forms of genomic instability. A lesion in DNA can block transcription (conversion of DNA to RNA) completely, it may truncate the transcript, or it may cause errors in the transcription. Alternatively, the DNA damage may induce new transcripts, and a number of genes have been shown to be inducible by various forms of cellular stress. These changes in transcription patterns that are caused by DNA damage may be part of the origin of the malignant phenotype; many changes in transcription have been reported in cancers. They are also likely to be a cause of some of the changes seen in aging, where reductions, or in some cases increases, in transcriptional activity are well established (Bohr and Anson). Lesions in DNA also can lead to cell cycle arrest, or they can cause strand breaks in DNA.
It is estimated that there are several thousand DNA alterations in each cell in the human organism per day (Lindahl), caused by both endogenous and exogenous stresses. Were it not for an efficient DNA repair process, genetic material would be destroyed by these processes over a normal human lifetime.
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