breast cancer type 1 susceptibility protein (BRCA1)
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Function
- role in DNA repair
- elevated levels at G1/S transition, peak in S phase, remain elevated into G2.
- phosphorylated at S phase
- role in response to DNA damage
- hyperphosphorylated in response to DNA damage induced by IR, UV, & various stimuli that cause checkpoint activation, probably by ATM or ATR
- involved in transcriptional regulation of P21 in response to DNA damage
- required for FANCD2 targeting to sites of DNA damage
- may function as a transcriptional regulator
- mediates E2-dependent ubiquitination
- inhibits lipid synthesis by binding to inactive phosphorylated ACACA & preventing its dephosphorylation
- part of the BRCA1-associated genome surveillance complex
- BRCA1 forms various molecular complexes:
- BASC (BRCA1 associated genome surveillance complex)
- BRCA1/BARD1/BRCC45/BRCC36
- BRCA1/BARD1 heterodimer - an E3 ubiquitin ligase
- BRCC holoenzyme complex
Structure
- RING-type Zn+2 finger domain interacts with BAP1
- contains 2 BRCT domains
- contains 1 RING-type Zn+2 finger
Compartment
Pathology
- defects in BRCA1 are a cause of genetic susceptibility
- 10-15% of non-familial breast cancers show hypermethylation of the BRCA1 gene.[3]
- rare form of Gln-356-Arg & Leu-871-Pro polymorphisms may be associated with an increased risk for developing ovarian cancer
- pathogenic variants in BRCA1 & BRCA2 are associated with increased risk of
Laboratory
More general terms
- transcription factor (TF)
- DNA-binding protein
- anti-oncoprotein (tumor suppressor protein)
- phosphoprotein
Component of
References
- ↑ UniProt http://www.uniprot.org/uniprot/P38398.html
- ↑ Zhang H, Tombline G, Weber BL. BRCA1, BRCA2, and DNA damage response: collision or collusion? Cell. 1998 Feb 20;92(4):433-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9491884
- ↑ 3.0 3.1 Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002 Jun;3(6):415-28. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12042769
- ↑ Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R. Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol Cell. 2003 Nov;12(5):1087-99. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14636569
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=672
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1 SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=BRCA1 Wikipedia; BRCA1 entry http://en.wikipedia.org/wiki/BRCA1
- ↑ 7.0 7.1 Momozawa Y et al. Expansion of cancer risk profile for BRCA1 and BRCA2 pathogenic variants. JAMA Oncol 2022 Apr 14; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/35420638 PMCID: PMC9011177 Free PMC article https://jamanetwork.com/journals/jamaoncology/fullarticle/2791277