RGD Reference Report - Phosphorylated BRCA1 is predominantly located in the nucleus and mitochondria. - Rat Genome Database

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Phosphorylated BRCA1 is predominantly located in the nucleus and mitochondria.

Authors: Coene, ED  Hollinshead, MS  Waeytens, AA  Schelfhout, VR  Eechaute, WP  Shaw, MK  Van Oostveldt, PM  Vaux, DJ 
Citation: Coene ED, etal., Mol Biol Cell. 2005 Feb;16(2):997-1010. Epub 2004 Dec 9.
RGD ID: 1599499
Pubmed: PMID:15591126   (View Abstract at PubMed)
PMCID: PMC545929   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E04-10-0895   (Journal Full-text)

Multiple copies of the mitochondrial genome in eukaryotic cells are organized into protein-DNA complexes called nucleoids. Mitochondrial genome repair mechanisms have been reported, but they are less well characterized than their nuclear counterparts. To expand our knowledge of mitochondrial genome maintenance, we have studied the localization of the BRCA1 protein, known to be involved in nuclear repair pathways. Our confocal and immunoelectron microscopy results show that BRCA1 is present in mitochondria of several human cancer cell lines and in primary breast and nasal epithelial cells. BRCA1 localization in mitochondria frequently overlapped that of nucleoids. Small interfering RNA-mediated knockdown of BRCA1 in human cancer cells (confirmed by Western blot) results in decreased nuclear, cytoplasmic, and mitochondrial staining after immunofluorescence microscopy, establishing the specificity of the BRCA1 immunolabeling. Furthermore, using cell fractionation, dephosphorylation, and enzyme protection experiments, we show that a 220-kDa phosphorylated isoform of BRCA1 is enriched in mitochondrial and nuclear fractions but reduced in cytoplasmic subcellular fractions. Submitochondrial fractionation confirmed the presence of BRCA1 protein in isolated mitoplasts. Because phosphorylation of BRCA1 and subsequent changes in subcellular localization are known to follow DNA damage, our data support a universal role for BRCA1 in the maintenance of genome integrity in both mitochondria and nucleus.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitochondrial matrix  IDA 1599499 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Brca1  (BRCA1, DNA repair associated)


Additional Information