DNA damage-binding protein or UV-DDB is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

complex that is responsible for repair of UV-damaged

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

. This complex is composed of two protein subunits, a large subunit

DDB1 DNA damage-binding protein 1 is a protein that in humans is encoded by the ''DDB1'' gene. Gene The gene's position is on chromosome 11q12-q13. Protein The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer compos ...

(p127) and a small subunit

DDB2 DNA damage-binding protein 2 is a protein that in humans is encoded by the ''DDB2'' gene. Structure As indicated by Rapić-Otrin et al. in 2003, the ''DDB2'' gene is located on human chromosome 11p11.2, spans a region of approximately 24 – 26 ...

(p48). When cells are exposed to

UV radiation Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of t ...

, 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 Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. Intercalation (biochemistry), intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single ...

, recognising UV-induced (6-4) pyrimidine-pyrimidone photoproducts and cyclobutane pyrimidine dimers.

Structure

The helical domain at the n-terminus of DDB2 binds to UV damaged DNA with high affinity to form the UV-DDB complex. The helical binding interaction at the n-terminus of DDB2 allows for the protein to bind immediately after detecting UV damaged DNA. DNA binds to DDB2 only when damaged by UV radiation. Binding with high affinity to a helical domain of DDB2 in the dimer form, UV-DDB, is facilitated by the n-terminal alpha helical paddle and beta wings of the DDB2 subunit. Both the alpha helical fold and the beta wing loops form a "winged helix" motif. The dimerized complex acts as a scaffold for DNA damage repair pathways and allows for other proteins to detect, interact, and repair UV damaged DNA.

DDB2

DDB2 is a protein part of the CUL4A–RING ubiquitin ligase (CRL4) complex. It was thought that DDB2 only acts to recognize legions of UV damaged DNA. It has been found that DDB2 plays a role in promoting chromatin unfolding. This role is independent of DDB2's role in the CRL4 complex.

Damage sensor role

UV-DDB is not only responsible for the repair of damaged DNA, it can also function by acting as a damage sensor. In base excision repair, UV-DDB galvanizes OGG1 and APE 1 activities. During DNA damage, proteins OGG1 and APE 1 encounter difficulty in repairing the lesions in a DNA wrapped nucleosome. Additionally, histones function by making the DNA inaccessible because of the way they make DNA coil and wrap into chromatin. UV-DDP plays a role in identifying the damaged sites within the chromatin, thereby allowing access to base excision repair proteins. When UV-DDB is recruited to these damaged sites, it recognizes the OGG1- AP DNA complex and further accelerates the turnover of glycosylases.

References

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