Apoptotic DNA fragmentation factor maintains chromosome stability in a P53-independent manner

Yan, Biao; Wang, H; Zhuo, Degen; F, Li; Kon, Takashi; Dewhirst, Mark W.; Cy, Li

doi:10.1038/sj.onc.1209535

Cited by 21 publications

(20 citation statements)

References 33 publications

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“…This proposal is further supported by the observations that the absence of DFF results in an increased frequency of cellular transformation of mouse embryonic fibroblasts and enhanced susceptibility to radiation induced carcinogenesis in DFF40-null mice [74]. Increased rates of radiation-induced chromosome instability and increased survival of irradiated DFF-deficient cells took place irrespectively of their p53 status [75]. Results from this model study are in complete agreement with data collected from human cancers.…”

Section: Dff As a Tumor Suppressorsupporting

confidence: 88%

“…Surprisingly, DFF null mice exhibit enhanced spatial learning and memory with longer memory retention compared to wild type controls; indeed, these null mice possess an increase in the number of granule cells in the dentate gyrus [114][115][116]. Most importantly, DFF null mice are at increased risk to develop cancer and have reduced genomic stability [74,75]. Finally, it is worth mentioning that DFF is not ubiquitously present among eukaryotes; for example, DFF is absent from Saccharomyces cerevisiae and C. elegans.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 93%

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Roles of the Major Apoptotic Nuclease-DNA Fragmentation Factor-in Biology and Disease

Widłak

Garrard

2008

Cell. Mol. Life Sci.

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It has now been more than ten years since the discovery of the major apoptotic nuclease, DNA fragmentation factor (DFF), also known as caspase-activated DNase (CAD). Here we review the recent literature that has uncovered new insight into DFF's regulation, and both its positive and negative roles in human disease. Cells from mice deficient in DFF still undergo apoptotic death without significant cell-autonomous DNA degradation. Their corpses' genomes are subsequently degraded by lysosomal DNase II after phagocytosis. However,DFF-deficient mice are more susceptible to cancer. Indeed, several different cancers in humans are associated with defects in DFF expression and it has been proposed that DFF is a p53-independent tumor suppressor. Negative aspects of DFF expression include contributing to susceptibility to acquire systemic lupus erythematosus, to chromosomal translocations that result in mixed lineage leukemias, and in the possible spreading of oncogenes and HIV due to horizontal gene transfer.

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Section: Dff As a Tumor Suppressorsupporting

confidence: 88%

Section: Conclusion and Future Perspectivesmentioning

confidence: 93%

Roles of the Major Apoptotic Nuclease-DNA Fragmentation Factor-in Biology and Disease

Widłak

Garrard

2008

Cell. Mol. Life Sci.

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“…Chromosome aberrations were scored as described previously (11). Please refer to Supplementary Data.…”

Section: Methodsmentioning

confidence: 99%

Tumor Necrosis Factor-α Is a Potent Endogenous Mutagen that Promotes Cellular Transformation

et al. 2006

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Tumor necrosis factor-A (TNF-A) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-A can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-A is comparable with that of ionizing radiation. TNF-A treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation, and chromosomal instability. Antioxidants significantly reduced TNF-A-induced genetic damage. TNF-A also induced oxidative stress and nucleotide damages in mouse tissues in vivo. Moreover, TNF-A treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. As TNF-A is involved in chronic inflammatory diseases, such as chronic hepatitis, ulcerative colitis, and chronic skin ulcers, and these diseases predispose the patients to cancer development, our results suggest a novel pathway through which TNF-A promotes cancer development through induction of gene mutations, in addition to the previously reported mechanisms, in which nuclear factor-KB activation was implicated. (Cancer Res 2006; 66(24): 11565-70)

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“…6). Similarly, the role of p53-independent apoptotic DNA fragmentation has been shown in maintaining chromosome stability and suppressing tumor development [43].…”

Section: The Structures Of the Compounds Shown Inmentioning

confidence: 99%

A synthetic uracil derivative with antitumor activity through decreasing cyclin D1 and Cdk1, and increasing p21 and p27 in MCF-7 cells

Marchal

Núñez

Suárez

et al. 2006

Breast Cancer Res Treat

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The anticarcinogenic potential of (RS)-1-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)uracil (DBDU), with the naturally occurring pyrimidine base uracil, is reported against the MCF-7 cancer cell line. The arrest in the G0/G1 and G2/M cell cycle phases was accounted for by decrease in the expression of the cyclin D1 and Cdk1 proteins, and increase in p21 and p27 proteins. Using a reverse transcription-polymerase chain reaction-based assay at a dose of 5 muM of DBDU cyclin D1 mRNA was decreased, suggesting that DBDU exerts its regulatory action on cyclin D1 at the level of transcription. DNA fragmentation was performed and demonstrated that apoptosis occurred in the tumor cell line treated with DBDU. The G0/G1 arrest is an irreversible process and the cells undergo apoptosis in a p53-independent manner. DBDU administered intravenously twice a week (50 mg/kg dose each time) induced neither toxicity nor death in mice for 5 weeks.

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Apoptotic DNA fragmentation factor maintains chromosome stability in a P53-independent manner

Cited by 21 publications

References 33 publications

Roles of the Major Apoptotic Nuclease-DNA Fragmentation Factor-in Biology and Disease

Roles of the Major Apoptotic Nuclease-DNA Fragmentation Factor-in Biology and Disease

Tumor Necrosis Factor-α Is a Potent Endogenous Mutagen that Promotes Cellular Transformation

A synthetic uracil derivative with antitumor activity through decreasing cyclin D1 and Cdk1, and increasing p21 and p27 in MCF-7 cells

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