Article

DNA-damage repair; the good, the bad, and the ugly. EMBO J

Department of Medical Biophysics, Ontario Cancer Institute/UHN, University of Toronto, Toronto, Ontario, Canada.
The EMBO Journal (Impact Factor: 10.75). 03/2008; 27(4):589-605. DOI: 10.1038/emboj.2008.15
Source: PubMed

ABSTRACT Organisms have developed several DNA-repair pathways as well as DNA-damage checkpoints to cope with the frequent challenge of endogenous and exogenous DNA insults. In the absence or impairment of such repair or checkpoint mechanisms, the genomic integrity of the organism is often compromised. This review will focus on the functional consequences of impaired DNA-repair pathways. Although each pathway is addressed individually, it is essential to note that cross talk exists between repair pathways, and that there are instances in which a DNA-repair protein is involved in more than one pathway. It is also important to integrate DNA-repair process with DNA-damage checkpoints and cell survival, to gain a better understanding of the consequences of compromised DNA repair at both cellular and organismic levels. Functional consequences associated with impaired DNA repair include embryonic lethality, shortened life span, rapid ageing, impaired growth, and a variety of syndromes, including a pronounced manifestation of cancer.

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    • "The other DNA repair system is base excision repair (BER), which allows the restoration of base damage and removes of different types of endogenous single strand breaks in DNA damage, including oxidative DNA base modifications like 8-oxoG arising from normal cellular metabolism and genotoxic agents such as ultraviolet A radiation, X-rays and alkylating agents (Memisoglu and Samson, 2000; Nilsen and Krokan, 2001). This process generates a basic (AP) site, which is further processed in a multistep process with slight differences depending on the type of damage (de Boer and Hoeijmakers, 2000; Christmann et al., 2003; Hakem, 2008; Camenisch and Naegeli, 2009). BER mainly corrects non-bulky lesions produced by alkylation, oxidation or deamination (Memisoglu and Samson, 2000; Nilsen and Krokan, 2001). "
    [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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    • "The other DNA repair system is base excision repair (BER), which allows the restoration of base damage and removes of different types of endogenous single strand breaks in DNA damage, including oxidative DNA base modifications like 8-oxoG arising from normal cellular metabolism and genotoxic agents such as ultraviolet A radiation, X-rays and alkylating agents (Memisoglu and Samson, 2000; Nilsen and Krokan, 2001). This process generates a basic (AP) site, which is further processed in a multistep process with slight differences depending on the type of damage (de Boer and Hoeijmakers, 2000; Christmann et al., 2003; Hakem, 2008; Camenisch and Naegeli, 2009). BER mainly corrects non-bulky lesions produced by alkylation, oxidation or deamination (Memisoglu and Samson, 2000; Nilsen and Krokan, 2001). "
    [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
    • "The other DNA repair system is base excision repair (BER), which allows the restoration of base damage and removes of different types of endogenous single strand breaks in DNA damage, including oxidative DNA base modifications like 8-oxoG arising from normal cellular metabolism and genotoxic agents such as ultraviolet A radiation, X-rays and alkylating agents (Memisoglu and Samson, 2000; Nilsen and Krokan, 2001). This process generates a basic (AP) site, which is further processed in a multistep process with slight differences depending on the type of damage (de Boer and Hoeijmakers, 2000; Christmann et al., 2003; Hakem, 2008; Camenisch and Naegeli, 2009). BER mainly corrects non-bulky lesions produced by alkylation, oxidation or deamination (Memisoglu and Samson, 2000; Nilsen and Krokan, 2001). "
    [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
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