Nuclear mitochondrial DNA activates replication in Saccharomyces cerevisiae.
Nuclear mitochondrial DNA activates replication in Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pone.0017235
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发表时间：
2011-03-08
期刊：
影响因子：
3.7
通讯作者：
Ricchetti M
中科院分区：
文献类型：
--
作者：
Chatre L;Ricchetti M
真核生物的核基因组由线粒体起源的DNA片段定植，称为NUMTs。这些插入与人类的多种生殖系疾病有关。这种将潜在危险的序列吸收到核基因组中的意义尚不清楚。在这里，我们提供了线粒体起源的序列促进酿酒酵母核DNA复制的功能证据。我们发现NUMT富含关键的自主复制序列(ARS)共识基序，其突变会导致DNA复制活性的降低或丧失。此外，对暴露于羟基脲的mrc1突变体的2D-Gel分析表明，有几个NUMT作为晚期染色体起源。我们还表明，位于ARS附近或ARS内的NUMT为复制提供了关键的序列元件。因此，当NUMT插入适当的基因组环境中或影响先前存在的起始点的效率时，它可以作为独立的起始点。这些发现表明，迁移性线粒体DNA可以影响它们所插入的核区域的复制。
The nuclear genome of eukaryotes is colonized by DNA fragments of mitochondrial origin, called NUMTs. These insertions have been associated with a variety of germ-line diseases in humans. The significance of this uptake of potentially dangerous sequences into the nuclear genome is unclear. Here we provide functional evidence that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae. We show that NUMTs are rich in key autonomously replicating sequence (ARS) consensus motifs, whose mutation results in the reduction or loss of DNA replication activity. Furthermore, 2D-gel analysis of the mrc1 mutant exposed to hydroxyurea shows that several NUMTs function as late chromosomal origins. We also show that NUMTs located close to or within ARS provide key sequence elements for replication. Thus NUMTs can act as independent origins, when inserted in an appropriate genomic context or affect the efficiency of pre-existing origins. These findings show that migratory mitochondrial DNAs can impact on the replication of the nuclear region they are inserted in.
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