Mitochondria as determinant of nucleotide pools and chromosomal stability
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Mitochondria as determinant of nucleotide pools and chromosomal stability. / Desler, Claus; Munch-Petersen, Birgitte; Stevnsner, Tinna; Matsui, Sei-Ichi; Kulawiec, Mariola; Singh, Keshav K; Rasmussen, Lene Juel.
In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 625, No. 1-2, 01.12.2007, p. 112-24.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mitochondria as determinant of nucleotide pools and chromosomal stability
AU - Desler, Claus
AU - Munch-Petersen, Birgitte
AU - Stevnsner, Tinna
AU - Matsui, Sei-Ichi
AU - Kulawiec, Mariola
AU - Singh, Keshav K
AU - Rasmussen, Lene Juel
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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.
AB - 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.
KW - Chromosomal Instability
KW - Comet Assay
KW - DNA Repair
KW - DNA, Mitochondrial
KW - Deoxyribonucleotides
KW - HeLa Cells
KW - Humans
KW - Micronucleus Tests
KW - Mitochondria
KW - Thymine Nucleotides
U2 - 10.1016/j.mrfmmm.2007.06.002
DO - 10.1016/j.mrfmmm.2007.06.002
M3 - Journal article
C2 - 17658559
VL - 625
SP - 112
EP - 124
JO - Mutation Research Letters
JF - Mutation Research Letters
SN - 0027-5107
IS - 1-2
ER -
ID: 119639828