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PMID:20413593

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Citation

Sage, JM, Gildemeister, OS and Knight, KL (2010) Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome. J. Biol. Chem. 285:18984-90

Abstract

Homologous recombination (HR) plays a critical role in facilitating replication fork progression when the polymerase complex encounters a blocking DNA lesion, and it also serves as the primary mechanism for error-free repair of DNA double strand breaks. Rad51 is the central catalyst of HR in all eukaryotes, and to this point studies of human Rad51 have focused exclusively on events occurring within the nucleus. However, substantial amounts of HR proteins exist in the cytoplasm, yet the function of these protein pools has not been addressed. Here, we provide the first demonstration that Rad51 and the related HR proteins Rad51C and Xrcc3 exist in human mitochondria. We show stress-induced increases in both the mitochondrial levels of each protein and, importantly, the physical interaction between Rad51 and mitochondrial DNA (mtDNA). Depletion of Rad51, Rad51C, or Xrcc3 results in a dramatic decrease in mtDNA copy number as well as the complete suppression of a characteristic oxidative stress-induced copy number increase. Our results identify human mtDNA as a novel Rad51 substrate and reveal an important role for HR proteins in the maintenance of the human mitochondrial genome.

Links

PubMed PMC2885175 Online version:10.1074/jbc.M109.099846

Keywords

Cell Cycle; Cell Line, Tumor; Cytoplasm/metabolism; DNA Breaks, Double-Stranded; DNA Damage; DNA, Mitochondrial/genetics; DNA-Binding Proteins/metabolism; Genome; Humans; Mitochondria/metabolism; Oxidative Stress; Rad51 Recombinase/genetics; Rad51 Recombinase/metabolism; Rad51 Recombinase/physiology; Subcellular Fractions/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:RA51C

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:XRCC3

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAD51

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RAD51

part_of

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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