DNA damage-binding protein

{{infobox protein

| Name = damage-specific DNA binding protein 1, 127kDa

| caption =

| image =

| width =

| 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

| caption =

| image =

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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

{{Reflist|refs=

{{cite journal | vauthors = Iovine B, Iannella ML, Bevilacqua MA | title = Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions | journal = The International Journal of Biochemistry & Cell Biology | volume = 43 | issue = 12 | pages = 1664–7 | date = December 2011 | pmid = 21959250 | doi = 10.1016/j.biocel.2011.09.001 | publisher = Elsevier }}

{{cite journal | vauthors = Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S | title = 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 | journal = Genomics | volume = 29 | issue = 1 | pages = 62–9 | date = September 1995 | pmid = 8530102 | doi = 10.1006/geno.1995.1215 }}

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