Drug Target and Biomarker: BRCA1 (G672)

NCBI ID: G672

BRCA1

Drug Target and Biomarker: BRCA1

BRCA1 haploinsufficiency leads to chromatin looping deficiency and impaired transcriptional activation.

BRCA1 is essential for mitophagy and its deficiency can result in the accumulation of damaged mitochondria and inflammation, contributing to tumorigenesis and cancer metastasis.

Long non-coding RNAs (lncRNAs) play a role in regulating the radioresistance of BRCA, potentially through mechanisms such as DNA repair, apoptosis, autophagy, cell cycle regulation, and others.

Mutated BRCA1 can lead to elevated R-loops at enhancer and/or promoter regions of luminal fate genes, downregulating their expression and potentially contributing to the formation of basal-like BRCA1-associated tumors.

BRCA1 is involved in subnetworks of genes mutated in ovarian carcinomas, including TP53, MYC, and CTNNB1, despite not being differentially expressed itself.

These viewpoints provide insights into the various roles and mechanisms involving BRCA1, such as its contribution to chromatin looping, mitophagy, radioresistance regulation, breast differentiation, and its relevance in ovarian carcinomas.
Based on the provided context information, several key viewpoints can be extracted regarding the role of BRCA1:

In wild-type cells, the MRE11 and EXO1 branch may be less prevalent compared to the DNA2/WRN branch, with an inhibitory feedback from WRN to MRE11 possibly contributing to this arrangement. However, in BRCA1 or BRCA2-defective cells, the MRE11 and EXO1 branch dominates, and WRN is no longer a contributor. This results in DNA breakage and increased DNA damage due to fork collapse and segregation of under-replicated DNA.

BRCA1 is involved in the regulation of DNA repair choice and interacts with UHRF1 to form a cascade that influences this process.

Depletion of BRCA1 leads to an increase in colocalized markers of defective replication, such as pATRThr1989 and pChk1S345, with TERRA RNA at telomeres. This suggests that BRCA1 is important for suppressing replication-associated telomeric damage and maintaining telomere integrity.

BRCA1 plays a role in suppressing and resolving R-loops at subtelomeric and telomeric regions, thereby modulating their heterochromatic state and preventing replication stress. Excessive TERRA levels and unresolved R-loops lead to replication stress, telomeric aberrancies, and telomere shortening.

Shieldin, which includes BRCA1 as a component, functions by binding to single-stranded DNA at double-strand break (DSB) sites and suppressing resection. This promotes non-homologous end joining (NHEJ) for DSB repair.

In the Fanconi anemia (FA) pathway of interstrand crosslink (ICL) repair, BRCA1 acts to dismantle the replisome and promotes the recruitment of nucleases for nucleolytic incisions. This facilitates lesion bypass and subsequent repair through homologous recombination (HR).

These viewpoints provide a comprehensive summary of the various roles and functions of BRCA1 in DNA repair, replication, and telomere integrity.

Protein Name: BRCA1 DNA Repair Associated

Functions: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:12887909, PubMed:10500182, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:12183412, PubMed:11836499, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719)

The "BRCA1 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about BRCA1 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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