DNA damage-binding protein or UV-DDB[1] is a protein complex that is responsible for repair of UV-damaged DNA.[2] 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.[3] This complex functions in nucleotide excision repair, recognising UV-induced (6-4) pyrimidine-pyrimidone photoproducts and cyclobutane pyrimidine dimers.[1]
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.[3] 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.[3] Both the alpha helical fold and the beta wing loops form a "winged helix" motif.[3] 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.[4] 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.[5] In base excision repair, UV-DDB galvanizes OGG1 and APE 1 activities.[5] 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.[5]
References
12Iovine B, Iannella ML, Bevilacqua MA (December 2011). "Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions". The International Journal of Biochemistry & Cell Biology. 43 (12). Elsevier: 1664–7. doi:10.1016/j.biocel.2011.09.001. PMID21959250.
↑Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S (September 1995). "Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein". Genomics. 29 (1): 62–9. doi:10.1006/geno.1995.1215. PMID8530102.
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