The importance of the proper functioning of the BER pathway, is shown in phenotype observed in knockout mice strains to sustain life. Is not compatible with life defects gross BER. In the knockout mouse of the gene encoding the essential BER proteins, including DNA ligase XRCC1, POLβ, APE/HAP1, and FEN1, I is embryonic lethal. However, other stages of the path BER may be protected by redundancy. On the other hand, if it shows a little phenotype found that showed high sensitivity to the occurrence of tumor MYH/OGG1 double mutant mice OGG1 knockout mice.
There is a hereditary disease of many people associated with the cellular response to a defective DNA damage. (In the example, including xeroderma pigmentosum, a trichothiodystrophy and Cockayne syndrome), response flawed basic NER (Nijmegen breakage syndrome and ataxia telangiectasia) helicase DNA strand break repair defect (colon, including the hereditary non-polyposis cancer) (Bloom, Rothmund-Thomson syndrome and Werner) mismatch repair, chromosome stability and (Fanconi anemia) class switch recombination (hyper IGM syndrome). Cancer susceptibility is a common theme among people with DNA repair gene mutations. Bound DNA damage and defects in DNA repair, can lead to tumor formation inevitable and genomic instability. The syndrome chromosome recessive familial cancer, such as xeroderma pigmentosum ataxia telangiectasia like this, Bloom syndrome, Fanconi anemia, Rothmund-Thomson, and Werner’s syndrome is likely to occur, defects in DNA repair in genomic instability It is an example of how that can lead.
Genetic disease caused by mutations in the gene BER pathway is less common than those caused other genes, by DNA repair pathway. Interestingly, however, in about half in response to a change in one amino acid 30% of all human tumors, I examined the protein POLβ embodiment. May have a mutation in the gene phenotypes family-like familial adenomatous polyposis, which encodes the human homolog of MutY has been shown, Cancer 2002 links, and between the defects is BER inherited the initial It is reported in the year. It decreased ability to initiate the repair of ,8-oxoG • mismatch that led mutations lead to inactivation of the protein adenomatous polyposis car probably, to increase the transformer version number of adenomatous polyposis gene car the GT MutY homolog discovery turned out to cause.
Recessive mutation of UNG is one of the reasons for the Hyper-IGM syndrome of primary immunodeficiency disease found it in three patients. The route is initiated by activation-induced cytidine deaminase, UNG is required to cause class switching antibody genes involved in the formation of high affinity antibodies and somatic recombination mutations. In these patients, recessive mutations have been found in the catalytic domain, which is shared by nuclear and mitochondrial isoforms of UNG. That B cells from patients with these severe, to impair the class switch recombination step precleavage DNA in patterns of somatic hypermutation is abnormal was found. 28% of the elderly (> 18 months), and UNG knockout mice developed a lymphoma compared with only 1.3% of the control animals, still, these patients do not progress to cancer.
Lymphoma, different mutations miscoding two LIG1 allele individual growth retardation, sun sensitivity, and was discovered in immunodeficiency (165) patients. Defect retardation connection Okazaki fragments lagging strand DNA synthesis represents an index, the patient-derived fibroblast cell line, increased sensitivity to DNA damaging agents in several ways.
Further mutation of the gene for DNA repair, it is associated with a neurodegenerative disease. As an example, Werner’s syndrome (WS) is included with (B and CSA) ataxia telangiectasia (ATM), xeroderma pigmentosum (XPA-G), Cockayne syndrome. In addition, as part of the syndrome, trichothiodystrophy, Rothmund-Thomson syndrome and Bloom syndrome, have mental retardation. This is believed to be capable of neurons in Alzheimer’s disease patients have a genetic defect in BER. In fact, 8 – increases the level of mitochondrial deletions and oxoG, lack BER has been found in patients with Alzheimer’s disease. Level of metabolism of the nerve cells is high, it may be the BER, compared to other types of cells (such as mitochondria and nuclei) repair of DNA damage in nerve cells plays a more important role has been proposed . Oxidative stress plays an important role in neuronal cell death associated with neurodegenerative diseases in various ways. Elevated levels of oxidative damage is observed in chronic active plaque of patients with multiple sclerosis and dementia and related area, of the brain with Lewy bodies of the cortex. In addition, isoforms of OGG1 mitochondria increases in substantia nigra and activity APE1 expression and patients with Parkinson’s disease has declined amyotrophic lateral sclerosis (ALS), in sporadic ALS patients. APE1 missense mutations sporadic, were found in 8 out of 11 cases of familial ALS patients. However, one report indicates that APE1 has increased in ALS patients.