Article

DNA mismatch repair: Molecular mechanism, cancer, and ageing

Genetics & Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mechanisms of Ageing and Development (Impact Factor: 3.51). 07/2008; 129(7-8):391-407. DOI: 10.1016/j.mad.2008.02.012
Source: PubMed

ABSTRACT DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.

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    • "Cadmium is able to sufficiently suppress the MMR system to abrogate the G2 cell cycle checkpoint arrest following alkylation damage (Bertin and Averbeck, 2006). This toxic element may escape G2 arrest and/or apoptosis following DNA damage, thus continuing proliferation of cells with genetic changes, the hallmark of cancer cells (Bertin and Averbeck, 2006).The MMR system also plays a key role in cell killing in response to alkylating agents, and MMR deficient cells are about 100 times more resistant to the cytotoxicity of alkylating agents (O'Brien and Brown, 2006; Hsieh and Yamane, 2008). "
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    ABSTRACT: Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancerrelated mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.
    Asian Pacific journal of cancer prevention: APJCP 02/2015; 16(1):9-21. · 2.51 Impact Factor
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    • "Cadmium is able to sufficiently suppress the MMR system to abrogate the G2 cell cycle checkpoint arrest following alkylation damage (Bertin and Averbeck, 2006). This toxic element may escape G2 arrest and/or apoptosis following DNA damage, thus continuing proliferation of cells with genetic changes, the hallmark of cancer cells (Bertin and Averbeck, 2006).The MMR system also plays a key role in cell killing in response to alkylating agents, and MMR deficient cells are about 100 times more resistant to the cytotoxicity of alkylating agents (O'Brien and Brown, 2006; Hsieh and Yamane, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancerrelated mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.
    Asian Pacific journal of cancer prevention: APJCP 02/2015; 16(1):9-21. · 2.51 Impact Factor
  • Source
    • "Cadmium is able to sufficiently suppress the MMR system to abrogate the G2 cell cycle checkpoint arrest following alkylation damage (Bertin and Averbeck, 2006). This toxic element may escape G2 arrest and/or apoptosis following DNA damage, thus continuing proliferation of cells with genetic changes, the hallmark of cancer cells (Bertin and Averbeck, 2006).The MMR system also plays a key role in cell killing in response to alkylating agents, and MMR deficient cells are about 100 times more resistant to the cytotoxicity of alkylating agents (O'Brien and Brown, 2006; Hsieh and Yamane, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancerrelated mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.
    Asian Pacific journal of cancer prevention: APJCP 02/2015; 16(1):9-21. DOI:10.7314/APJCP.2015.16.1.9 · 2.51 Impact Factor
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