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Publication : The Mitochondrial DNA Polymerase Promotes Elimination of Paternal Mitochondrial Genomes.

First Author  Yu Zhongsheng Year  2017
Journal  Curr. Biol. Volume  27
Pages  1033-1039 PubMed ID  28318978
Abstract Text  Mitochondrial DNA (mtDNA) is typically inherited from only one parent [1-3]. In animals, this is usually the mother. Maternal inheritance is often presented as the passive outcome of the difference in cytoplasmic content of egg and sperm; however, active programs enforce uniparental inheritance at two levels, eliminating paternal mitochondrial genomes or destroying mitochondria delivered to the zygote by the sperm [4-13]. Both levels operate in Drosophila [8, 12, 13]. As sperm formation begins, hundreds of doomed mitochondrial genomes are visualized within the two huge mitochondria of each spermatid. These genomes abruptly disappear during spermatogenesis. Genome elimination, which is not in the interests of the restricted genomes, is directed by nuclear genes. Mutation of EndoG, which encodes a mitochondria-targeted endonuclease, retarded elimination [8]. Here, we show that knockdown of the nuclear-encoded mtDNA polymerase (Pol γ-α), Tamas, produces a more complete block of mtDNA elimination. Tamas is found in large particles that localize to mtDNA during genome elimination. We discount a simple possible mechanism by showing that the 3'-exonuclease function of the polymerase is not needed. While DNA elimination is a surprising function for DNA polymerase, it could provide a robust nexus for nuclear control of mitochondrial genome copy number, since use of common interactions for elimination and replication might limit options for the mitochondrial genome to escape restriction. We suggest that the DNA polymerase may play this role more widely and that inappropriate activation of its elimination ability might underlie association of DNA loss syndromes with mutations of the human mtDNA polymerase [14-16]. Doi  10.1016/j.cub.2017.02.014
Issue  7 Month  Apr

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