Search results for DDB2

Showing 19 results out of 30

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Species

Types

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Protein (3 results from a total of 3)

Identifier: R-HSA-53491
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: DDB2: Q92466
Identifier: R-HSA-5696654
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: DDB2: Q92466
Identifier: R-HSA-6783035
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: DDB2: Q92466

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-6806606
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENSG00000134574

Reaction (6 results from a total of 11)

Identifier: R-HSA-5696997
Species: Homo sapiens
Compartment: nucleoplasm
USP24 deubiquitinates DDB2, which is involved in the nucleotide excision repair pathway, preventing its proteasomal degradation (Zhang et al. 2012).
Identifier: R-HSA-6806417
Species: Homo sapiens
Compartment: nucleoplasm
TP53 (p53) binds the p53 response element in the 5'UTR-encoding region of the DDB2 gene. The p53 response element is present in the human DDB2 gene, but absent from the mouse Ddb2 gene (Tan and Chu 2002).
Identifier: R-HSA-6806423
Species: Homo sapiens
Compartment: nucleoplasm
TP53 (p53) stimulates transcription of the DDB2 gene, involved in nucleotide excision repair, by binding to the p53 response element in the 5'UTR-encoding region of the DDB2 gene (Tan and Chu 2002).
Identifier: R-HSA-5696655
Species: Homo sapiens
Compartment: nucleoplasm
PARP1 and/or PARP2 homo- or heterodimers recruited to global genomic nucleotide excision repair (GG-NER) site poly(ADP)ribosylate (PARylate) DDB2 and also progressively autoPARylate. PARylation promotes retention of DDB2 at DNA damage sites (Pines et al. 2012, Robu et al. 2013).
Identifier: R-HSA-5696664
Species: Homo sapiens
Compartment: nucleoplasm
PARP1 (or PARP2) is recruited to global genomic nucleotide excision repair (GG-NER) site through interaction with DDB2 and, probably, distorted single strand DNA (Pines et al. 2012, Robu et al. 2013).
Identifier: R-HSA-5691006
Species: Homo sapiens
Compartment: nucleoplasm
XPC, in complex with RAD23B or RAD23A and CETN2, employs a two-stage process to recognize a distorted DNA helix. In the first stage, XPC rapidly probes dsDNA, which is promoted by a DNA repulsive action of a negatively charged beta-turn extension of XPC, located in the vicinity of the XPC DNA-binding domain. In the second stage, the DNA binding domain, consisting of two beta hairpins, binds non-hydrogen bonded bases in dsDNA (Camenisch et al. 2009). Rad4, the yeast ortholog of XPC, recognizes lesions that thermodynamically disrupt normal Watson-Crick base pairing. Rad4 inserts a beta-hairpin through the DNA duplex, causing damaged base pairs to flip out of the double helix. Rad4 associates with the undamaged strand, whereas the DNA strand that contains damaged nucleotides becomes distorted (Min and Pavletich 2007).

Binding of the XPC:RAD23:CETN2 complex to distorted DNA is enhanced in the presence of the DDB1:DDB2 complex, also known as the UV-DDB complex. The UV-DDB complex preferentially binds UV-generated lesions, such as pyrimidine-pyrimidone photodimers (6-4 PPDs) and cyclobutane pyrimidine dimers (CPDs), but also recognizes DNA with apurinic/apyrimidinic (AP) sites, and 2-3 bp mismatches (Fujiwara et al. 1999, Wittschieben et al. 2005). The DDB2 subunit of the UV-DDB complex is a WD40 repeat beta-propeller protein. The beta-propeller domain of DDB2 binds the damaged DNA strand (Scrima et al. 2008). The UV-DDB complex is part of a larger ubiquitin ligase complex that, besides DDB1 and DDB2, also contains CUL4A or CUL4B and RBX1 (Groisman et al. 2003, Sugasawa et al. 2005). In the case of 6-4 PPDs and CPDs, UV-DDB binding to damaged DNA probably precedes the binding of the XPC:RAD23:CETN2 complex. However, in the case of 6-4 PPDs, the XPC:RAD23:CETN2 complex may also recognize damaged DNA in the absence of the UV-DDB complex (Fitch et al. 2003, Moser et al. 2005, Wang et al. 2004), but the UV-DDB complex may be important for retention of DNA repair proteins at the DNA damage site (Oh et al. 2011).

The INO80 chromatin remodelling complex positively regulates GG-NER. INO80 and ACTR5 (ARP5) subunits of the INO80 complex are enriched at GG-NER sites, probably via interaction with DDB1. Chromatin relaxation by the INO80 complex at DNA damage site may be necessary for XPC recruitment (Jiang et al. 2010). In yeast, the interaction between INO80 and the orthologs of XPC and RAD23 has been reported and it was suggested that this interaction is important for the restoration of chromatin structure after GG-NER completion (Sarkar et al. 2010).

Complex (6 results from a total of 12)

Identifier: R-HSA-5688955
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6783054
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5696680
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6783041
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-6806601
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5696649
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (3 results from a total of 3)

Identifier: R-HSA-5696394
Species: Homo sapiens
Compartment: nucleoplasm
In global genome nucleotide excision repair (GG-NER), the DNA damage is recognized by two protein complexes. The first complex consists of XPC, RAD23A or RAD23B, and CETN2. This complex probes the DNA helix and recognizes damage that disrupts normal Watson-Crick base pairing, which results in binding of the XPC:RAD23:CETN2 complex to the undamaged DNA strand. The second complex is a ubiquitin ligase UV-DDB that consists of DDB2, DDB1, CUL4A or CUL4B and RBX1. The UV-DDB complex is necessary for the recognition of UV-induced DNA damage and may contribute to the retention of the XPC:RAD23:CETN2 complex at the DNA damage site. The UV-DDB complex binds the damaged DNA strand (Fitch et al. 2003, Wang et al. 2004, Moser et al. 2005, Camenisch et al. 2009, Oh et al. 2011).
Identifier: R-HSA-6796648
Species: Homo sapiens
Several DNA repair genes contain p53 response elements and their transcription is positively regulated by TP53 (p53). TP53-mediated regulation probably ensures increased protein level of DNA repair genes under genotoxic stress.

TP53 directly stimulates transcription of several genes involved in DNA mismatch repair, including MSH2 (Scherer et al. 2000, Warnick et al. 2001), PMS2 and MLH1 (Chen and Sadowski 2005). TP53 also directly stimulates transcription of DDB2, involved in nucleotide excision repair (Tan and Chu 2002), and FANCC, involved in the Fanconi anemia pathway that repairs DNA interstrand crosslinks (Liebetrau et al. 1997). Other p53 targets that can influence DNA repair functions are RRM2B (Kuo et al. 2012), XPC (Fitch et al. 2003), GADD45A (Amundson et al. 2002), CDKN1A (Cazzalini et al. 2010) and PCNA (Xu and Morris 1999). Interestingly, the responsiveness of some of these DNA repair genes to p53 activation has been shown in human cells but not for orthologous mouse genes (Jegga et al. 2008, Tan and Chu 2002). Contrary to the positive modulation of nucleotide excision repair (NER) and mismatch repair (MMR), p53 can negatively modulate base excision repair (BER), by down-regulating the endonuclease APEX1 (APE1), acting in concert with SP1 (Poletto et al. 2016).

Expression of several DNA repair genes is under indirect TP53 control, through TP53-mediated stimulation of cyclin K (CCNK) expression (Mori et al. 2002). CCNK is the activating cyclin for CDK12 and CDK13 (Blazek et al. 2013). The complex of CCNK and CDK12 binds and phosphorylates the C-terminal domain of the RNA polymerase II subunit POLR2A, which is necessary for efficient transcription of long DNA repair genes, including BRCA1, ATR, FANCD2, FANCI, ATM, MDC1, CHEK1 and RAD51D. Genes whose transcription is regulated by the complex of CCNK and CDK12 are mainly involved in the repair of DNA double strand breaks and/or the Fanconi anemia pathway (Blazek et al. 2011, Cheng et al. 2012, Bosken et al. 2014, Bartkowiak and Greenleaf 2015, Ekumi et al. 2015).

Identifier: R-HSA-5696399
Species: Homo sapiens
Compartment: nucleoplasm
The DNA damage in GG-NER is recognized by the joint action of two protein complexes. The first complex is composed of XPC, RAD23A or RAD23B and CETN2. The second complex, known as the UV-DDB complex, is an ubiquitin ligase composed of DDB1, CUL4A or CUL4B, RBX1 and a GG-NER specific protein DDB2. In vitro, the UV-DDB complex is onlynecessary for GG-NER mediated repair of UV-induced pyrimidine dimers. In vivo, however, where DNA repair occurs in the chromatin context, the UV-DDB complex likely facilitates GG-NER mediated repair irrespective of the DNA damage type.
After DNA damage recognition, the TFIIH complex, together with XPA, verifies the DNA damage and unwinds the DNA helix around the damage, creating an open bubble. Two DNA endonucleases, ERCC5 (XPG) and the complex of ERCC1 and ERCC4 (XPF), excise the oligonucleotide that contains damaged base(s) from the affected DNA strand. DNA polymerases delta, epsilon and/or kappa perform DNA repair synthesis, followed by DNA ligation, thus completing GG-NER.
For a recent review, please refer to Marteijn et al. 2014.
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