Reactome | BRCA1 forms a heterodimer with BARD1

BRCA1 forms a heterodimer with BARD1

Stable Identifier

R-HSA-5659781

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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BRCA1 and BARD1 form a stable heterodimer through an interaction between sequences encompassing their N-terminal RING domains (Wu et al. 1996, Brzovic et al. 2001). In addition to the RING domains, BRCA1 and BARD1 both have tandem BRCT motifs at their C termini. The central region of BARD1 contains ankyrin repeats (Wu et al. 1996). Formation of BRCA1:BARD1 heterodimers is necessary for the repair of double-strand DNA breaks by homologous recombination (Westermark et al. 2003, Laufer et al. 2007), BRCA1-mediated tumor suppression (Shakya et al. 2008) and normal development (McCarthy et al. 2003). Tumorigenic BRCA1 mutations that abolish the formation of BRCA1:BARD1 heterodimers have been reported (Wu et al. 1996, Brzovic et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
18443292	The basal-like mammary carcinomas induced by Brca1 or Bard1 inactivation implicate the BRCA1/BARD1 heterodimer in tumor suppression Shakya, R, Szabolcs, M, McCarthy, E, Ospina, E, Basso, K, Nandula, S, Murty, V, Baer, RJ, Ludwig, T	Proc. Natl. Acad. Sci. U.S.A.	2008
17848578	Structural requirements for the BARD1 tumor suppressor in chromosomal stability and homology-directed DNA repair Laufer, M, Nandula, SV, Modi, AP, Wang, S, Jasin, M, Murty, VV, Ludwig, T, Baer, RJ	J. Biol. Chem.	2007
11573085	Structure of a BRCA1-BARD1 heterodimeric RING-RING complex Brzovic, PS, Rajagopal, P, Hoyt, DW, King, MC, Klevit, RE	Nat. Struct. Biol.	2001
8944023	Identification of a RING protein that can interact in vivo with the BRCA1 gene product Wu, LC, Wang, ZW, Tsan, JT, Spillman, MA, Phung, A, Xu, XL, Yang, MC, Hwang, LY, Bowcock, AM, Baer, R	Nat. Genet.	1996
14560035	BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks Westermark, UK, Reyngold, M, Olshen, AB, Baer, RJ, Jasin, M, Moynahan, ME	Mol. Cell. Biol.	2003
12832489	Loss of Bard1, the heterodimeric partner of the Brca1 tumor suppressor, results in early embryonic lethality and chromosomal instability McCarthy, EE, Celebi, JT, Baer, RJ, Ludwig, T	Mol. Cell. Biol.	2003