Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes
Autor: | Simon Wisnovsky, Sae Rin Jean, Sanduni Liyanage, Aaron Schimmer, Shana O Kelley |
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Rok vydání: | 2016 |
Předmět: |
DNA Replication
0301 basic medicine Mitochondrial DNA DNA Repair DNA repair Eukaryotic DNA replication DNA-Directed DNA Polymerase Biology DNA Mitochondrial Mitochondrial Proteins DNA replication factor CDT1 03 medical and health sciences 0302 clinical medicine Control of chromosome duplication Humans Molecular Biology Replication protein A Genetics DNA replication Cell Biology Cell biology Oxidative Stress 030104 developmental biology Mitochondrial DNA repair Molecular Probes 030220 oncology & carcinogenesis biology.protein DNA Damage |
Zdroj: | Nature Chemical Biology. 12:567-573 |
ISSN: | 1552-4469 1552-4450 |
DOI: | 10.1038/nchembio.2102 |
Popis: | Efficient and accurate replication and repair of mitochondrial DNA is essential for cellular viability, yet only a minimal complement of mitochondrial proteins with relevant activities have been identified. Here, we describe an approach to screen for new pathways involved in the maintenance of mitochondrial DNA (mtDNA) that leverages the activities of DNA-damaging probes exhibiting specific subcellular localization. By conducting a siRNA screen of known nuclear DNA maintenance factors, and monitoring synergistic effects of gene depletion on the activity of mitochondria-specific DNA-damaging agents, we identify a series of proteins not previously recognized to act within mitochondria. These include proteins that function in pathways of oxidative DNA damage repair and dsDNA break repair, along with a novel mitochondrial DNA polymerase, POLθ, that facilitates efficient DNA replication in an environment prone to oxidative stress. POLθ expression levels affect the mutational rate of mitochondrial DNA, but this protein also appears critical for efficient mtDNA replication. |
Databáze: | OpenAIRE |
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