DNA damage-binding protein
{{infobox protein
| Name = damage-specific DNA binding protein 1, 127kDa
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| image =
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| HGNCid = 2717
| Symbol = DDB1
| AltSymbols = XPE
| EntrezGene = 1642
| OMIM = 600045
| RefSeq = NM_001923
| UniProt = Q16531
| PDB =
| ECnumber =
| Chromosome = 11
| Arm = q
| Band = 12
| LocusSupplementaryData = -q13
}}
{{infobox protein
| Name = damage-specific DNA binding protein 2, 48kDa
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| HGNCid = 2718
| Symbol = DDB2
| AltSymbols = DBB, UV-DDB2, FLJ34321
| EntrezGene = 1643
| OMIM = 600811
| RefSeq = NM_000107
| UniProt = Q92466
| PDB =
| ECnumber =
| Chromosome = 11
| Arm = p
| Band = 12
| LocusSupplementaryData = -p11
}}
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.{{cite journal | vauthors = Yeh JI, Levine AS, Du S, Chinte U, Ghodke H, Wang H, Shi H, Hsieh CL, Conway JF, Van Houten B, Rapić-Otrin V | display-authors = 6 | title = Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) dimerization and its roles in chromatinized DNA repair | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 41 | pages = E2737-46 | date = October 2012 | pmid = 22822215 | doi = 10.1073/pnas.1110067109 | pmc = 3478663 | doi-access = free }} This complex functions in nucleotide excision repair, 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.{{cite journal | vauthors = Luijsterburg MS, Lindh M, Acs K, Vrouwe MG, Pines A, van Attikum H, Mullenders LH, Dantuma NP | display-authors = 6 | title = DDB2 promotes chromatin decondensation at UV-induced DNA damage | journal = The Journal of Cell Biology | volume = 197 | issue = 2 | pages = 267–81 | date = April 2012 | pmid = 22492724 | doi = 10.1083/jcb.201106074 | pmc = 3328393 | doi-access = free }} 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.{{cite journal | vauthors = Jang S, Kumar N, Beckwitt EC, Kong M, Fouquerel E, Rapić-Otrin V, Prasad R, Watkins SC, Khuu C, Majumdar C, David SS, Wilson SH, Bruchez MP, Opresko PL, Van Houten B | display-authors = 6 | title = Damage sensor role of UV-DDB during base excision repair | journal = Nature Structural & Molecular Biology | volume = 26 | issue = 8 | pages = 695–703 | date = August 2019 | pmid = 31332353 | doi = 10.1038/s41594-019-0261-7 | pmc = 6684372 }} 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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