Mitochondrial DNA mutators

被引:26
作者
Foury, F [1 ]
Hu, J [1 ]
Vanderstraeten, S [1 ]
机构
[1] Catholic Univ Louvain, Unite Biochim Physiol, B-1348 Louvain, Belgium
关键词
base excision repair; mismatch repair; mitochondria; mutator; oxidative damage; PEO; Pol gamma; yeast;
D O I
10.1007/s00018-004-4220-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this article we review our current knowledge of the mechanisms by which point mutations arise in the mitochondrial DNA ( mtDNA) of Saccharomyces cerevisiae and discuss to what extent these mechanisms operate in human mtDNA mutagenesis. The 3'-5' exonuclease proofreading activity of Pol gamma ensures accuracy of mtDNA replication in both yeast and humans, while the role of base excision repair in mtDNA error avoidance remains debated. The mitochondrial mismatch repair Msh1 protein, which removes transitions in yeast, is absent in humans, a particularity that might cause accumulation of transitions, while the most frequent substitution in yeast mtDNA is A: T to T: A transversion. Proofreading-deficient mutator human cell lines and knockin mice have been created. They will be useful for studying the mechanisms by which mtDNA mutations accumulate in diseases, ageing, malignancy and drug therapy.
引用
收藏
页码:2799 / 2811
页数:13
相关论文
共 83 条
[1]  
Alseth I, 1999, MOL CELL BIOL, V19, P3779
[2]   SEQUENCE AND ORGANIZATION OF THE HUMAN MITOCHONDRIAL GENOME [J].
ANDERSON, S ;
BANKIER, AT ;
BARRELL, BG ;
DEBRUIJN, MHL ;
COULSON, AR ;
DROUIN, J ;
EPERON, IC ;
NIERLICH, DP ;
ROE, BA ;
SANGER, F ;
SCHREIER, PH ;
SMITH, AJH ;
STADEN, R ;
YOUNG, IG .
NATURE, 1981, 290 (5806) :457-465
[3]  
Bebenek K, 1995, METHOD ENZYMOL, V262, P217
[4]   STRUCTURE OF DNA-POLYMERASE-I KLENOW FRAGMENT BOUND TO DUPLEX DNA [J].
BEESE, LS ;
DERBYSHIRE, V ;
STEITZ, TA .
SCIENCE, 1993, 260 (5106) :352-355
[5]   Base miscoding and strand misalignment errors by mutator klenow polymerases with amino acid substitutions at tyrosine 766 in the O helix of the fingers subdomain [J].
Bell, JB ;
Eckert, KA ;
Joyce, CM ;
Kunkel, TA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (11) :7345-7351
[6]   A CONSERVED 3'-]5' EXONUCLEASE ACTIVE-SITE IN PROKARYOTIC AND EUKARYOTIC DNA-POLYMERASES [J].
BERNAD, A ;
BLANCO, L ;
LAZARO, JM ;
MARTIN, G ;
SALAS, M .
CELL, 1989, 59 (01) :219-228
[7]   Mitochondrial genome instability in human cancers [J].
Bianchi, NO ;
Bianchi, MS ;
Richard, SM .
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2001, 488 (01) :9-23
[8]   Repair of mtDNA in vertebrates [J].
Bogenhagen, DF .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (05) :1276-1281
[9]   Abasic sites in DNA:: repair and biological consequences in Saccharomyces cerevisiae [J].
Boiteux, S ;
Guillet, M .
DNA REPAIR, 2004, 3 (01) :1-12
[10]   Mammalian mitochondrial DNA replicates bidirectionally from an initiation zone [J].
Bowmaker, M ;
Yang, MY ;
Yasukawa, T ;
Reyes, A ;
Jacobs, HT ;
Huberman, JA ;
Holt, IJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (51) :50961-50969