BRCA1-C complex

Definition

Target type: cellularcomponent

A protein complex that contains the BRCA1-BARD1 heterodimer, CtIP and Mre11/Rad50/NBS1 (M/R/N) complex, and binds to DNA at DNA damage sites. BRCA1-C binding ta damaged DNA is required for DNA damage-induced Chk1 phosphorylation and the G2/M transition checkpoint. [GOC:mah, PMID:15485915, PMID:16391231]

The BRCA1-C complex is a multi-protein complex that plays a crucial role in DNA repair, particularly in homologous recombination (HR) repair. It functions as a scaffold, bringing together various proteins involved in the HR pathway to facilitate accurate and efficient DNA damage repair. The complex's cellular component is primarily localized to the nucleus, specifically at sites of DNA double-strand breaks (DSBs). This strategic location allows the complex to quickly respond to DNA damage and initiate the HR repair process.

The core components of the BRCA1-C complex include:

* **BRCA1:** This protein serves as the central scaffold of the complex. It possesses multiple domains that interact with various partner proteins, including PALB2, RAD51, and CtIP. BRCA1 plays a critical role in recognizing DSBs, recruiting other repair factors, and promoting the assembly of the complex.
* **PALB2:** This protein acts as a bridge between BRCA1 and BRCA2, two key players in HR repair. PALB2 interacts with both proteins, stabilizing their association and enhancing their function. It also contributes to DNA damage sensing and the recruitment of RAD51.
* **BRCA2:** This protein is essential for RAD51 filament formation, a crucial step in HR repair. BRCA2 interacts with RAD51 and facilitates its loading onto single-stranded DNA, enabling homologous recombination to occur.

Besides these core components, the BRCA1-C complex also incorporates other accessory proteins, including:

* **CtIP:** This protein works alongside BRCA1 to promote resection of DSB ends, generating single-stranded DNA that can be used as a template for HR repair.
* **RAD51:** This protein forms filaments on single-stranded DNA and catalyzes the search for homologous DNA sequences, facilitating the exchange of genetic information during HR repair.
* **MRE11-RAD50-NBS1 (MRN) complex:** This complex acts upstream of BRCA1 and plays a crucial role in sensing DNA damage and initiating the DNA repair process.

The BRCA1-C complex's intricate organization and dynamic interplay with its partner proteins enable it to effectively promote accurate DNA repair through homologous recombination. This ensures the stability of the genome and protects cells from accumulating harmful mutations, which could ultimately lead to cancer development. Understanding the cellular component of the BRCA1-C complex provides crucial insights into the molecular mechanisms of DNA repair and highlights its importance in maintaining genomic integrity.'
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Proteins (2)

Compounds (1)