Base excision repair and the role of MUTYH
نویسندگان
چکیده
The correction of exogenous and endogenous environmental insult to DNA involves a series of DNA repair mechanisms that reduce the likelihood of mutation accumulation and hence an increased probability of tumour development. The mechanisms underlying the process of base excision repair are relatively well understood and are placed in context with how deterioration of this process is associated with an increased risk of malignancy.
منابع مشابه
MutYH (MYH) and colorectal cancer.
MAP (MutYH-associated polyposis) is a recently described colorectal adenoma and carcinoma predisposition syndrome that is associated with biallelic-inherited mutations of the human MutY homologue gene, MutYH. MutYH is often also termed MYH. MAP tumours display a mutational signature of somatic guanine-to-thymine transversion mutations in the adenomatous polyposis coli and K-ras genes, reflectin...
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In 2002, Al-Tassan and co-workers described for the first time a recessive form of inherited polyposis associated with germline mutations of MUTYH, a gene encoding a base excision repair (BER) protein that counteracts the DNA damage induced by the oxidative stress. MUTYH-associated polyposis (MAP) is now a well-defined cancer susceptibility syndrome, showing peculiar molecular features that cha...
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COLORECTAL CANCER IS CLASSIFIED IN TO THREE FORMS sporadic (70-75%), familial (20-25%) and hereditary (5-10%). hereditary colorectal cancer syndromes classified into two different subtypes: polyposis and non polyposis. Familial Adenomatous polyposis (FAP; OMIM #175100) is the most common polyposis syndrome, account for <1% of colorectal cancer incidence and characterized by germline mutations i...
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MUTYH is a DNA repair enzyme that initiates a base excision repair (BER) by recognizing and removing 8-Oxoguanine (8-oxoG) and its paired adenine. We demonstrated that both TGF-β1 and H2O2 treatment led to an increased 8-oxoG in cultured human proximal tubule epithelial (HK-2) cells, while the former induced epithelial-mesenchymal transition and the latter caused cell apoptosis. Without stimula...
متن کامل8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair.
8-Oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species, is associated with carcinogenesis and neurodegeneration. Although the mechanism by which 8-oxoG causes carcinogenesis is well understood, the mechanism by which it causes neurodegeneration is unknown. Here, we report that neurodegeneration is triggered by MUTYH-mediated excision repair of 8-oxoG-paired adenine. Mutant...
متن کاملRole of MUTYH and MSH2 in the control of oxidative DNA damage, genetic instability, and tumorigenesis.
Mismatch repair is the major pathway controlling genetic stability by removing mispairs caused by faulty replication and/or mismatches containing oxidized bases. Thus, inactivation of the Msh2 mismatch repair gene is associated with a mutator phenotype and increased cancer susceptibility. The base excision repair gene Mutyh is also involved in the maintenance of genomic integrity by repairing p...
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ورودعنوان ژورنال:
- Hereditary Cancer in Clinical Practice
دوره 5 شماره
صفحات -
تاریخ انتشار 2007