DDB - damage specific DNA binding protein | Elisa - Clia - Antibody - Protein

Background

Damage specific DNA binding protein (DDB) is a crucial component of the nucleotide excision repair (NER) pathway, responsible for recognizing and initiating the repair of DNA lesions caused by UV radiation and other genotoxic agents. The DDB complex, primarily composed of DDB1 and DDB2 (also known as XPE), plays a pivotal role in the early stages of DNA damage recognition. Upon detecting DNA damage, particularly cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts, DDB facilitates the recruitment of other NER factors to the damaged site, thereby promoting efficient DNA repair and maintaining genomic stability.

Protein Structure

• DDB1: Composed of approximately 1140 amino acids, DDB1 features multiple WD40 repeat domains which form a β-propeller structure, facilitating interactions with various proteins, including DDB2 and components of the ubiquitin-proteasome system.
• DDB2: Smaller than DDB1, DDB2 consists of about 427 amino acids and contains a unique domain known as the UV-damaged DNA binding domain, which is essential for recognizing UV-induced DNA lesions.

Classification and Subtypes

DDB proteins are classified based on their involvement in DNA repair pathways and their interaction with other proteins. The primary members of the DDB family are:

• DDB1 (Damage-Specific DNA Binding Protein 1): Acts as a scaffold protein in the DDB complex and interacts with various other proteins, including DDB2 and components of the ubiquitin ligase complex.
• DDB2 (Damage-Specific DNA Binding Protein 2): Specifically binds to UV-damaged DNA and is crucial for the initial recognition of DNA lesions.

Function and Biological Significance

• DNA Damage Recognition: DDB2 recognizes and binds to UV-induced DNA lesions, such as CPDs and 6-4 photoproducts, marking the site for repair.
• Recruitment of Repair Factors: Upon binding to damaged DNA, the DDB complex recruits other NER factors, such as XPC, to the damage site, initiating the repair process.
• Regulation of NER: DDB1, as part of the CUL4-DDB1 E3 ubiquitin ligase complex, ubiquitinates various proteins involved in DNA repair, thereby regulating their stability and activity.
• Cell Cycle Control and Transcription Regulation: Beyond DNA repair, DDB1 interacts with transcription factors and cell cycle regulators, influencing cellular responses to DNA damage.

Clinical Issues

• Xeroderma Pigmentosum (XP): Mutations in DDB2 are associated with Xeroderma Pigmentosum group E (XP-E), a condition characterized by extreme sensitivity to UV light and a predisposition to skin cancers.
• Cancer: Defective DDB function can lead to impaired DNA repair, resulting in genomic instability and increased susceptibility to various cancers. Overexpression or aberrant regulation of DDB components has been observed in multiple cancer types.
• Aging and Degenerative Diseases: Inefficient DNA repair due to dysfunctional DDB proteins is linked to accelerated aging and the development of age-related degenerative diseases.

Summary

Damage specific DNA binding proteins (DDBs) are integral to the nucleotide excision repair (NER) pathway, primarily recognizing and initiating repair of UV-induced DNA lesions. The DDB complex, composed of DDB1 and DDB2, binds to damaged DNA and recruits other repair factors, facilitating the repair process. DDB1 and DDB2 have distinct structures and functions, with DDB1 acting as a scaffold protein and DDB2 specifically recognizing DNA damage. Defects in DDB function are associated with disorders such as Xeroderma Pigmentosum and various cancers, highlighting their importance in maintaining genomic stability and cellular homeostasis.