Shadel G S, Clayton D A
Department of Biochemistry, Emory University School of Medicine, Rollins Research Center, Atlanta, Georgia 30322, USA.
Annu Rev Biochem. 1997;66:409-35. doi: 10.1146/annurev.biochem.66.1.409.
The discovery that mutations in mitochondrial DNA (mtDNA) can be pathogenic in humans has increased interest in understanding mtDNA maintenance. The functional state of mtDNA requires a great number of factors for gene expression, DNA replication, and DNA repair. These processes are ultimately controlled by the cell nucleus, because the requisite proteins are all encoded by nuclear genes and imported into the mitochondrion. DNA replication and transcription are linked in vertebrate mitochondria because RNA transcripts initiated at the light-strand promoter are the primers for mtDNA replication at the heavy-strand origin. Study of this transcription-primed DNA replication mechanism has led to isolation of key factors involved in mtDNA replication and transcription and to elucidation of unique nucleic acid structures formed at this origin. Because features of a transcription-primed mechanism appear to be conserved in vertebrates, a general model for initiation of vertebrate heavy-strand DNA synthesis is proposed. In many organisms, mtDNA maintenance requires not only faithful mtDNA replication, but also mtDNA repair and recombination. The extent to which these latter two processes are involved in mtDNA maintenance in vertebrates is also appraised.
线粒体DNA(mtDNA)突变可在人类中致病这一发现,增加了人们对理解mtDNA维持机制的兴趣。mtDNA的功能状态需要大量参与基因表达、DNA复制和DNA修复的因子。这些过程最终由细胞核控制,因为所需的蛋白质均由核基因编码并导入线粒体。在脊椎动物线粒体中,DNA复制和转录相互关联,因为从轻链启动子起始的RNA转录本是重链起点处mtDNA复制的引物。对这种转录引发的DNA复制机制的研究,已导致参与mtDNA复制和转录的关键因子的分离,并阐明了在此起点形成的独特核酸结构。由于转录引发机制的特征在脊椎动物中似乎是保守的,因此提出了脊椎动物重链DNA合成起始的通用模型。在许多生物体中,mtDNA的维持不仅需要忠实的mtDNA复制,还需要mtDNA修复和重组。本文还评估了后两个过程在脊椎动物mtDNA维持中的参与程度。