Mutation analysis of the hMTH1 gene in sporadic human ovarian cancer.

Takama, Fumiko; Kanuma, Tatsuya; Wang, D.; Nishida, Jun‐ichi; Nakabeppu, Yusaku; Wake, Norio; Mizunuma, Hideki

doi:10.3892/ijo.17.3.467

Cited by 5 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MTH17/7 mice exhibit slightly elevated tumour incidence than wildtype mice but their survival at 1.5 years is not affected. Several studies on human cancers show that mutations in hMTH1 gene, so far are not involved in these pathologies (Wu et al, 1995;Takama et al, 2000). Unexpectedly, MTH1 and translesional DNA polymerase kappa (Pol-k) expressions were found to significantly increase and decrease respectively in two mammary carcinoma cell lines characterised by frequent A/T?G/C transversions (Okochi et al, 2002).…”

Section: Homologous Recombination Repair Pathwaymentioning

confidence: 99%

Enzymology of the repair of free radicals-induced DNA damage

2002

View full text Add to dashboard Cite

A number of intrinsic and extrinsic mutagens induce structural damage in cellular DNA. These DNA damages are cytotoxic, miscoding or both and are believed to be at the origin of cell lethality, tissue degeneration, ageing and cancer. In order to counteract immediately the deleterious effects of such lesions, leading to genomic instability, cells have evolved a number of DNA repair mechanisms including the direct reversal of the lesion, sanitation of the dNTPs pools, mismatch repair and several DNA excision pathways including the base excision repair (BER) nucleotide excision repair (NER) and the nucleotide incision repair (NIR). These repair pathways are universally present in living cells and extremely well conserved. This review is focused on the repair of lesions induced by free radicals and ionising radiation. The BER pathway removes most of these DNA lesions, although recently it was shown that other pathways would also be efficient in the removal of oxidised bases. In the BER pathway the process is initiated by a DNA glycosylase excising the modified and mismatched base by hydrolysis of the glycosidic bond between the base and the deoxyribose of the DNA, generating a free base and an abasic site (AP-site) which in turn is repaired since it is cytotoxic and mutagenic.

show abstract

Section: Homologous Recombination Repair Pathwaymentioning

confidence: 99%

Enzymology of the repair of free radicals-induced DNA damage

2002

View full text Add to dashboard Cite

show abstract

“…Consistently with this assumption, MTH1-knockout mice showed a higher incidence of lung, liver and stomach cancer (Tsuzuki et al, 2001a;2001b). However, no mutations or polymorphisms in the hMTH1 gene were found to be correlated with hereditary nonpolyposis colorectal cancer (HNPCC) (Wu et al, 1995), acute childhood leukemia (Lin et al, 1998b), hepatocellular carcinoma, lung cancer (Oda et al, 1999), ovarian cancer (Takama et al, 2000), familial adenomatous polyposis (FAP), sporadic colorectal cancer (Sieber et al, 2003;Kim et al, 2004), nor with Parkinson's disease (Satoh & Kuroda, 2000). Similarly, no such correlation was found in the rat 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)induced mammary carcinomas, which showed an elevated level of AT→CG transversions (Okochi et al, 2002a;2002b).…”

Section: Role Of Hmth1 In Human Diseasementioning

confidence: 74%

Bacterial DNA repair genes and their eukaryotic homologues: 2. Role of bacterial mutator gene homologues in human disease. Overview of nucleotide pool sanitization and mismatch repair systems.

Arczewska

Kuśmierek

2007

Acta Biochim Pol

View full text Add to dashboard Cite

Since the discovery of the first E. coli mutator gene, mutT, most of the mutations inducing elevated spontaneous mutation rates could be clearly attributed to defects in DNA repair. MutT turned out to be a pyrophosphohydrolase hydrolyzing 8-oxodGTP, thus preventing its incorporation into DNA and suppresing the occurrence of spontaneous AT-->CG transversions. Most of the bacterial mutator genes appeared to be evolutionarily conserved, and scientists were continuously searching for contribution of DNA repair deficiency in human diseases, especially carcinogenesis. Yet a human MutT homologue--hMTH1 protein--was found to be overexpressed rather than inactivated in many human diseases, including cancer. The interest in DNA repair contribution to human diseases exploded with the observation that germline mutations in mismatch repair (MMR) genes predispose to hereditary non-polyposis colorectal cancer (HNPCC). Despite our continuously growing knowledge about DNA repair we still do not fully understand how the mutator phenotype contributes to specific forms of human diseases.

show abstract

“…This hypothesis has evolved over time, with better understanding of the molecular basis for tumorigenesis, and it is now known that a mutator phenotype results from mutations in genes that maintain genome stability (8)(9)(10)(11)(12)(13). The recently identified germ-line and somatic mutations of POLE and POLD, which encode DNA polymerases e and δ, respectively, and which are associated with hypermutated tumors, provide additional strong evidence for the mutator phenotype hypothesis.…”

mentioning

confidence: 99%