کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2147273 | 1548404 | 2007 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mitochondria as determinant of nucleotide pools and chromosomal stability
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Mitochondrial function plays an important role in multiple human diseases and mutations in the mitochondrial genome have been detected in nearly every type of cancer investigated to date. However, the mechanism underlying the interrelation is unknown. We used human cell lines depleted of mitochondrial DNA as models and analyzed the outcome of mitochondrial dysfunction on major cellular repair activities. We show that the deoxyribonucleoside triphosphate (dNTP) pools are affected, most prominently we detect a 3-fold reduction of the dTTP pool when normalized to the number of cells in S-phase. It is known that imbalanced dNTP pools are mutagenic and in accordance, we show that mitochondrial dysfunction results in chromosomal instability, which can explain its role in tumor development. We did not find any straightforward correlation between ATP levels and dNTP pools in cells with defective mitochondrial activity. Our results suggest that mitochondria are central players in maintaining genomic stability and in controlling essential nuclear processes such as upholding a balanced supply of nucleotides.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 625, Issues 1â2, 1 December 2007, Pages 112-124
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 625, Issues 1â2, 1 December 2007, Pages 112-124
نویسندگان
Claus Desler, Birgitte Munch-Petersen, Tinna Stevnsner, Sei-Ichi Matsui, Mariola Kulawiec, Keshav K. Singh, Lene Juel Rasmussen,