DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene. [5] [6] [7]
DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene. [5] [6] [7]
The gene's position is on chromosome 11q12-q13. [8]
The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer composed of a large and a small (DDB2) subunit. DDB1 contains 1140 amino acids, amounting to a mass of 127 kDa. [8]
As its name suggests, DDB1 was initially implicated in the process of a specific type of DNA repair known as nucleotide excision repair. Since then, researchers have found that DDB1 primarily functions as a core component of the CUL4A- and CUL4B-based E3 ubiquitin ligase complexes. DDB1 serves as a bridge or adaptor protein which interacts with dozens of proteins known as DDB1 and CUL4-associated factors (DCAFs). [9] These DCAFs are often ubiquitin ligase substrates and regulate numerous essential processes in the cell including DNA repair (DDB2), DNA replication, chromatin remodeling (Cdt2) and more.
DDB1 has been shown to interact with Transcription initiation protein SPT3 homolog, [10] GCN5L2, [11] DDB2, [12] [13] CUL4A, [13] CUL4B [13] and P21. [14]
Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun-exposed areas, dry skin and changes in skin pigmentation. Nervous system problems, such as hearing loss, poor coordination, loss of intellectual function and seizures, may also occur. Complications include a high risk of skin cancer, with about half having skin cancer by age 10 without preventative efforts, and cataracts. There may be a higher risk of other cancers such as brain cancers.
UV excision repair protein RAD23 homolog A is a protein that in humans is encoded by the RAD23A gene.
COP9 signalosome complex subunit 6 is a protein that in humans is encoded by the COPS6 gene.
Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.
DNA damage-binding protein 2 is a protein that in humans is encoded by the DDB2 gene.
Transcription initiation factor TFIID subunit 6 is a protein that in humans is encoded by the TAF6 gene.
Xeroderma pigmentosum, complementation group C, also known as XPC, is a protein which in humans is encoded by the XPC gene. XPC is involved in the recognition of bulky DNA adducts in nucleotide excision repair. It is located on chromosome 3.
Transcription initiation factor TFIID subunit 12 is a protein that in humans is encoded by the TAF12 gene.
Transcription initiation factor TFIID subunit 4 is a protein that in humans is encoded by the TAF4 gene.
Transcription initiation factor TFIID subunit 2 is a protein that in humans is encoded by the TAF2 gene.
Transcription initiation factor TFIID subunit 10 is a protein that in humans is encoded by the TAF10 gene.
Transcription initiation factor TFIID subunit 5 is a protein that in humans is encoded by the TAF5 gene.
Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.
AP-1 complex subunit gamma-like 2 is a protein that in humans is encoded by the AP1G2 gene.
DNA polymerase eta, is a protein that in humans is encoded by the POLH gene.
Protein VPRBP is a protein that in humans is encoded by the VPRBP gene.
Vpr is a Human immunodeficiency virus gene and protein product. Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for virus replication and enhanced gene expression from provirus in dividing or non-dividing cells such as T cells or macrophages. Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.
HBx is a hepatitis B viral protein. It is 154 amino acids long and interferes with transcription, signal transduction, cell cycle progress, protein degradation, apoptosis and chromosomal stability in the host. It forms a heterodimeric complex with its cellular target protein, and this interaction dysregulates centrosome dynamics and mitotic spindle formation. It interacts with DDB1 redirecting the ubiquitin ligase activity of the CUL4-DDB1 E3 complexes, which are intimately involved in the intracellular regulation of DNA replication and repair, transcription and signal transduction.
Cereblon is a protein that in humans is encoded by the CRBN gene. The gene that encodes the cereblon protein is found on the human chromosome 3, on the short arm at position p26.3 from base pair 3,190,676 to base pair 3,221,394. CRBN orthologs are highly conserved from plants to humans.
DNA damage-binding protein or UV-DDB is a protein complex that is responsible for repair of UV-damaged DNA. This complex is composed of two protein subunits, a large subunit DDB1 (p127) and a small subunit DDB2 (p48). When cells are exposed to UV radiation, DDB1 moves from the cytosol to the nucleus and binds to DDB2, thus forming the UV-DDB complex. This complex formation is highly favorable and it is demonstrated by UV-DDB's binding preference and high affinity to the UV lesions in the DNA. This complex functions in nucleotide excision repair, recognising UV-induced (6-4) pyrimidine-pyrimidone photoproducts and cyclobutane pyrimidine dimers.
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| Excision repair | |
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| Homologous recombination | |
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