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Curr Opin Genet Dev. 2016 Jun;38:52-62. doi: 10.1016/j.gde.2016.03.005. Epub 2016 Apr 9.

Human mitochondrial DNA replication machinery and disease.

Author information

1
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, United States.
2
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, United States. Electronic address: copelan1@niehs.nih.gov.

Abstract

The human mitochondrial genome is replicated by DNA polymerase γ in concert with key components of the mitochondrial DNA (mtDNA) replication machinery. Defects in mtDNA replication or nucleotide metabolism cause deletions, point mutations, or depletion of mtDNA. The resulting loss of cellular respiration ultimately induces mitochondrial genetic diseases, including mtDNA depletion syndromes (MDS) such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. Here we review the current literature regarding human mtDNA replication and heritable disorders caused by genetic changes of the POLG, POLG2, Twinkle, RNASEH1, DNA2, and MGME1 genes.

PMID:
27065468
PMCID:
PMC5055853
DOI:
10.1016/j.gde.2016.03.005
[Indexed for MEDLINE]
Free PMC Article

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