DNA Repair and Tumor Formation

Due to the many damaging influences on the DNA, it is essential for the cell that DNA damage can be repaired. The repair systems involved, such as the enzyme apparatus of excision repair, the alkyl transferases and the mispairing repair system, operate almost without error and can repair the vast majority of DNA damage. A deficit in the repair 

These observations support the theory that, in an early stage of tumor formation, a mutation occurs in a repair system needed to maintain the integrity of the genome (Loeb, 1991, Loeb, 1998). Loss of the fimction of the repair system leads to a mutator phenotype a missing or ineffective DNA repair favors further accumulation of mutations and leads to an intrinsic instability of the genome. 

Genetic instability due to breakdown of a repair component is only seen in a small fraction of tumors, however. In the majority of tumors, instabUity at the level of the chromosomes can be established, which is manifested in loss or gain of whole chromosomes or large parts thereof This instability is associated with failure at cell cycle checkpoints (see 13.7,14.4.2). 

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