DNA damage-binding protein 2

Definition:

Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also functions as the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB2-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB2-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. The DDB2-CUL4-ROC1 complex also ubiquitinates KAT7/HBO1 in response to DNA damage, leading to its degradation: recognizes KAT7/HBO1 following phosphorylation by ATR.; [Isoform D1]: Inhibits UV-damaged DNA repair.; [Isoform D2]: Inhibits UV-damaged DNA repair.

References:

[1]. Kaoru Sugasawa, et al. UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. Cell. 2005 May 6;121(3):387-400. [Content Brief]

[2]. J Y Tang, et al. Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis. Mol Cell. 2000 Apr;5(4):737-44. [Content Brief]

[3]. Anke Geng, et al. The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2. Nucleic Acids Res. 2020 Sep 18;48(16):9181-9194. [Content Brief]

[4]. Maureen E Fitch, et al. In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product. J Biol Chem. 2003 Nov 21;278(47):46906-10. [Content Brief]

[5]. Taeko Inoki, et al. Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair. Biochem Biophys Res Commun. 2004 Feb 20;314(4):1036-43. [Content Brief]

[6]. Hengbin Wang, et al. Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol Cell. 2006 May 5;22(3):383-94. [Content Brief]

[7]. B J Hwang, et al. Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):424-8. [Content Brief]

[8]. Ryoichi Matsunuma, et al. UV Damage-Induced Phosphorylation of HBO1 Triggers CRL4DDB2-Mediated Degradation To Regulate Cell Proliferation. Mol Cell Biol. 2015 Nov 16;36(3):394-406. [Content Brief]

[9]. Mitsuo Wakasugi, et al. DDB accumulates at DNA damage sites immediately after UV irradiation and directly stimulates nucleotide excision repair. J Biol Chem. 2002 Jan 18;277(3):1637-40. [Content Brief]

[10]. Jennifer Guerrero-Santoro, et al. The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A. Cancer Res. 2008 Jul 1;68(13):5014-22. [Content Brief]

[11]. Regina Groisman, et al. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. [Content Brief]

[12]. M Wakasugi, et al. Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A. J Biol Chem. 2001 May 4;276(18):15434-40. [Content Brief]

[13]. Maria G Kapetanaki, et al. The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2588-93. [Content Brief]

[14]. Gülnihal Kulaksiz, et al. Xeroderma pigmentosum complementation group E protein (XPE/DDB2): purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties. Mol Cell Biol. 2005 Nov;25(22):9784-92. [Content Brief]

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