Mitochondria as determinant of nucleotide pools and chromosomal stability

Claus Desler Madsen; Birgitte Munch-Petersen; Tinna Stevnsner; Sei-Ichi Matsui; Keshav Singh; Mariola Kulawiec; Lene Juel Rasmussen

doi:10.1016/j.mrfmmm.2007.06.002

Mitochondria as determinant of nucleotide pools and chromosomal stability

Claus Desler Madsen, Birgitte Munch-Petersen, Tinna Stevnsner, Sei-Ichi Matsui, Keshav Singh, Mariola Kulawiec, Lene Juel Rasmussen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Udgivelsesdato: December

Originalsprog	Engelsk
Tidsskrift	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Vol/bind	625
Udgave nummer	1-2
Sider (fra-til)	112-124
Antal sider	13
ISSN	0027-5107
DOI	https://doi.org/10.1016/j.mrfmmm.2007.06.002
Status	Udgivet - 2007

Bibliografisk note

Paper id:: 17658559

Emneord

Kræft

Link til dokument

10.1016/j.mrfmmm.2007.06.002

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T2C-4P0DJX1-1-F&_cdi=4915&_user=1577482&_orig=browse&_coverDate=12%2F01%2F2007&_sk=993749998&view=c&wchp=dGLbVtb-zSkWz&md5=38d637106947d711891367a34b043b51&ie=/sdarticle.pdf

Citer dette

@article{b5d482a0af0611dc93d5000ea68e967b,

title = "Mitochondria as determinant of nucleotide pools and chromosomal stability",

abstract = "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.",

keywords = "Kr{\ae}ft, Mitochondrial disease, Cancer, Chromosomal instability, DNA repair, dNTP levels",

author = "Madsen, {Claus Desler} and Birgitte Munch-Petersen and Tinna Stevnsner and Sei-Ichi Matsui and Keshav Singh and Mariola Kulawiec and Rasmussen, {Lene Juel}",

note = "Paper id:: 17658559",

year = "2007",

doi = "10.1016/j.mrfmmm.2007.06.002",

language = "English",

volume = "625",

pages = "112--124",

journal = "Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis",

issn = "0027-5107",

publisher = "Elsevier BV",

number = "1-2",

}

TY - JOUR

T1 - Mitochondria as determinant of nucleotide pools and chromosomal stability

AU - Madsen, Claus Desler

AU - Munch-Petersen, Birgitte

AU - Stevnsner, Tinna

AU - Matsui, Sei-Ichi

AU - Singh, Keshav

AU - Kulawiec, Mariola

AU - Rasmussen, Lene Juel

N1 - Paper id:: 17658559

PY - 2007

Y1 - 2007

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 - Kræft

KW - Mitochondrial disease

KW - Cancer

KW - Chromosomal instability

KW - DNA repair

KW - dNTP levels

U2 - 10.1016/j.mrfmmm.2007.06.002

DO - 10.1016/j.mrfmmm.2007.06.002

M3 - Journal article

SN - 0027-5107

VL - 625

SP - 112

EP - 124

JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

IS - 1-2

ER -