BRCT domain

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PDB 1cdz EBI

BRCT Domain

The BRCT domain is a conserved protein domain found in a variety of proteins involved in DNA damage response and repair mechanisms. The acronym BRCT stands for BRCA1 C Terminus, as the domain was first identified in the BRCA1 tumor suppressor protein.

Structure

The BRCT domain is typically around 100 amino acids in length and forms a compact globular structure. It consists of a tandem repeat of two BRCT motifs, each containing a characteristic fold with conserved residues critical for protein-protein interactions and binding to phosphorylated residues on target proteins.

Function

Proteins containing BRCT domains are involved in various cellular processes, including DNA damage sensing, signaling, and repair. The BRCT domain acts as a phospho-protein binding module, recognizing phosphorylated serine or threonine residues on target proteins to facilitate protein-protein interactions and the assembly of DNA repair complexes.

Role in DNA Damage Response

In response to DNA damage, proteins with BRCT domains are recruited to sites of damage where they participate in the repair process. The BRCT domain plays a crucial role in mediating interactions between DNA repair proteins, ensuring the proper coordination of repair pathways and maintenance of genomic stability.

Clinical Relevance

Mutations in genes encoding proteins with BRCT domains have been associated with various human diseases, including cancer predisposition syndromes. Disruption of BRCT domain function can impair DNA repair mechanisms, leading to genomic instability and increased susceptibility to cancer development.

Examples of Proteins with BRCT Domains

- BRCA1: The BRCA1 protein contains two tandem BRCT domains that are essential for its tumor suppressor function. - BRCA2: Another tumor suppressor protein, BRCA2, also contains a BRCT domain that is involved in DNA repair processes. - MDC1: Mediator of DNA damage checkpoint protein 1 is a key regulator of the DNA damage response and contains multiple BRCT domains.