Hum Mol Genet 2003,
PMID: 12915460
Hussain, Shobbir; Witt, Emily; Huber, Pia A J; Medhurst, Annette L; Ashworth, Alan; Mathew, Christopher G
Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterized by progressive bone marrow failure, multiple congenital abnormalities, and an increased risk of cancer. FA cells are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. At least eight complementation groups exist (FA-A to G), and the genes for all of these except FA-B have been cloned. Functional linkage between the FA pathway and genes involved in susceptibility to breast cancer has been demonstrated by the interaction of the FANCA and FANCD2 proteins with BRCA1, and the discovery that the FANCD1 gene is identical to BRCA2. Here we have used the yeast two-hybrid system to test for direct interaction between BRCA2 or its effector RAD51 and the FANCA, FANCC and FANCG proteins. We found that FANCG was capable of binding to two separate sites in the BRCA2 protein, located either side of the BRC repeats. Furthermore, FANCG could be co-immunoprecipitated with BRCA2 from human cells, and FANCG co-localized in nuclear foci with both BRCA2 and RAD51 following DNA damage with mitomycin C. These results demonstrate that BRCA2 is directly connected to a pathway that is deficient in interstrand crosslink repair, and that at least one other FA protein is closely associated with the homologous recombination DNA repair machinery.
Diseases/Pathways annotated by Medline MESH: Fanconi Anemia
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Text Mining Data
Dashed line = No text mining data
Manually curated Databases
-
IRef Bind Interaction:
BRCA2
—
FANCG
-
IRef Bind_translation Interaction:
BRCA2
—
FANCG
(unspecified method)
-
IRef Bind_translation Interaction:
BRCA2
—
FANCG
(coimmunoprecipitation)
-
IRef Bind_translation Interaction:
BRCA2
—
FANCG
(two hybrid)
-
IRef Biogrid Interaction:
BRCA2
—
FANCG
(direct interaction, two hybrid)
-
IRef Biogrid Interaction:
BRCA2
—
FANCG
(physical association, affinity chromatography technology)
-
IRef Hprd Interaction:
RAD51
—
FANCG
(in vitro)
-
IRef Hprd Interaction:
RAD51
—
FANCG
(in vivo)
-
IRef Hprd Interaction:
RAD51
—
FANCG
(two hybrid)
-
NCI Pathway Database Fanconi anemia pathway:
BRCA2 (BRCA2)
→
FANCG (FANCG)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
BRCA2 (BRCA2)
→
XRCC3 (XRCC3)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
BRCA2 (BRCA2)
→
FANCD2 (FANCD2)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
BRCA2 (BRCA2)
→
FANCG/BRCA2/FANCD2/XRCC3 complex (FANCG-BRCA2-FANCD2-XRCC3)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
FANCG (FANCG)
→
XRCC3 (XRCC3)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
FANCG (FANCG)
→
FANCD2 (FANCD2)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
FANCG (FANCG)
→
FANCG/BRCA2/FANCD2/XRCC3 complex (FANCG-BRCA2-FANCD2-XRCC3)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
XRCC3 (XRCC3)
→
FANCD2 (FANCD2)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
XRCC3 (XRCC3)
→
FANCG/BRCA2/FANCD2/XRCC3 complex (FANCG-BRCA2-FANCD2-XRCC3)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Fanconi anemia pathway:
FANCD2 (FANCD2)
→
FANCG/BRCA2/FANCD2/XRCC3 complex (FANCG-BRCA2-FANCD2-XRCC3)
(modification, collaborate)
Evidence: mutant phenotype, physical interaction
In total, 11 gene pairs are associated to this article in curated databases