Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome

Student Author(s)

Jay M. Sage

UMMS Affiliation

Department of Biochemistry & Molecular Pharmacology

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences


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.

DOI of Published Version



Sage, J.M., Gildemeister, O.S. and Knight, K.L. (2010) Discovery of a Novel Function for Human Rad51: Maintenance of the Mitochondrial Genome. J. Biol. Chem. 285, 18984-18990.

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to article in PubMed

PubMed ID