DNA damage-binding protein

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]

damage-specific DNA binding protein 1, 127kDa
Identifiers
Symbol	DDB1
Alt. symbols	XPE
NCBI gene	1642
HGNC	2717
OMIM	600045
RefSeq	NM_001923
UniProt	Q16531
Other data
Locus	Chr. 11 q12-q13
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damage-specific DNA binding protein 2, 48kDa
Identifiers
Symbol	DDB2
Alt. symbols	DBB, UV-DDB2, FLJ34321
NCBI gene	1643
HGNC	2718
OMIM	600811
RefSeq	NM_000107
UniProt	Q92466
Other data
Locus	Chr. 11 p12-p11
Search for Structures Swiss-model Domains InterPro

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.^[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]