DNA damage-binding protein 1

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 a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) 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. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1. DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver (By similarity).

References:

[1]. Courtney A Lovejoy, et al. DDB1 maintains genome integrity through regulation of Cdt1. Mol Cell Biol. 2006 Nov;26(21):7977-90. [Content Brief]

[2]. J Huang, et al. VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene. 2008 Jul 3;27(29):4056-64. [Content Brief]

[3]. Eric S Fischer, et al. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature. 2014 Aug 7;512(7512):49-53. [Content Brief]

[4]. Yan Mo, et al. SIRT7 deacetylates DDB1 and suppresses the activity of the CRL4 E3 ligase complexes. FEBS J. 2017 Nov;284(21):3619-3636. [Content Brief]

[5]. Ingrid E Wertz, et al. Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science. 2004 Feb 27;303(5662):1371-4. [Content Brief]

[6]. 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]

[7]. Hideo Nishitani, et al. Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. EMBO J. 2006 Mar 8;25(5):1126-36. [Content Brief]

[8]. Jian Hu, et al. Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol. 2004 Oct;6(10):1003-9. [Content Brief]

[9]. Jian Hu, et al. WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes Dev. 2008 Apr 1;22(7):866-71. [Content Brief]

[10]. Eric S Fischer, et al. The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation. Cell. 2011 Nov 23;147(5):1024-39. [Content Brief]

[11]. Takeshi Senga, et al. PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. J Biol Chem. 2006 Mar 10;281(10):6246-52. [Content Brief]

[12]. Yizhou Joseph He, et al. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev. 2006 Nov 1;20(21):2949-54. [Content Brief]

[13]. Leigh Ann Higa, et al. CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat Cell Biol. 2006 Nov;8(11):1277-83. [Content Brief]

[14]. 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]

[15]. Ti Li, et al. A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. Nat Struct Mol Biol. 2010 Jan;17(1):105-11. [Content Brief]

[16]. Philip P Chamberlain, et al. Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014 Sep;21(9):803-9. [Content Brief]

[17]. 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]

[18]. Xin Tong, et al. CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activity by Promoting Ubiquitination-Dependent Degradation of the Mammalian CRY1. PLoS One. 2015 Oct 2;10(10):e0139725. [Content Brief]

[19]. 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]

[20]. 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]

[21]. Jian Hu, et al. An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage. J Biol Chem. 2006 Feb 17;281(7):3753-6. [Content Brief]

[22]. 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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