Inhibition of Transient Gene Expression in Chinese, Hamster Ovary Cells by Triplet‐sensitized Uv‐b Irradiation of Transfected Dna

Mitchell, David L.; Adair, Gerald M.; Nairn, Rodney S.

doi:10.1111/j.1751-1097.1989.tb04320.x

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…In humans, unrepaired lesions might potentially introduce oncogenic mutations and are a major cause of skin carcinogenesis (Hoeijmakers, 2009). Among the lesions caused by UV light, cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6–4) pyrimidinone dimers (6-4PPs) are the most common ones, accounting for 75% and 25% of DNA lesions, respectively, being able to stall RNAPII during transcription, which largely alters gene expression and cell functions (Mitchell et al, 1989; Fischer et al, 2011). Contrary to photoreactivation, dark repair pathways do not directly reverse DNA damage, but instead replace the damaged DNA with new, undamaged nucleotides.…”

Section: Dna Lesion Detection and Repair – Light As A Damagementioning

confidence: 99%

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

Fonseca

Rubio

2019

Front. Plant Sci.

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CULLIN4 (CUL4) RING ligase (CRL4) complexes contain a CUL4 scaffold protein, associated to RBX1 and to DDB1 proteins and have traditionally been associated to protein degradation events. Through DDB1, these complexes can associate with numerous DCAF proteins, which directly interact with specific targets promoting their ubiquitination and subsequent degradation by the proteasome. A characteristic feature of the majority of DCAF proteins that associate with DDB1 is the presence of the DWD motif. DWD-containing proteins sum up to 85 in the plant model species Arabidopsis. In the last decade, numerous Arabidopsis DWD proteins have been studied and their molecular functions uncovered. Independently of whether their association with CRL4 has been confirmed or not, DWD proteins are often found as components of additional multimeric protein complexes that play key roles in essential nuclear events. For most of them, the significance of their complex partnership is still unexplored. Here, we summarize recent findings involving both confirmed and putative CRL4-associated DCAF proteins in regulating nuclei architecture remodelling, DNA damage repair, histone post-translational modification, mRNA processing and export, and ribosome biogenesis, that definitely have an impact in gene expression and de novo protein synthesis. We hypothesized that, by maintaining accurate levels of regulatory proteins through targeted degradation and transcriptional control, CRL4 complexes help to surveil nuclear processes essential for plant development and survival.

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Section: Dna Lesion Detection and Repair – Light As A Damagementioning

confidence: 99%

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

Fonseca

Rubio

2019

Front. Plant Sci.

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“…Unrepaired lesions require error-prone translesion polymerases in S phase (Friedberg, 2001), which potentially introduce oncogenic mutations. Cyclobutane pyrimidine dimers (CPD) and (6-4) pyrimidine-pyrimidone photoproducts (6-4PP) are the two major photo-lesions, accounting for approximately 75% and 25% of genomic UV lesions, respectively (Mitchell et al, 1989). Compared to 6-4PP, CPDs cause relatively minor thermodynamic duplex destabilization (Jing et al, 1998), and are found frequently obscured by organization into nucleosomes (Gale and Smerdon, 1988).…”

Section: Introductionmentioning

confidence: 99%

The Molecular Basis of CRL4DDB2/CSA Ubiquitin Ligase Architecture, Targeting, and Activation

Fischer

Scrima

Böhm

et al. 2011

Cell

398

489

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The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs). The DCAF DDB2 detects UV-induced pyrimidine dimers in the genome and facilitates nucleotide excision repair. We provide the molecular basis for DDB2 receptor-mediated cyclobutane pyrimidine dimer recognition in chromatin. The structures of the fully assembled DDB1-DDB2-CUL4A/B-RBX1 (CRL4(DDB2)) ligases reveal that the mobility of the ligase arm creates a defined ubiquitination zone around the damage, which precludes direct ligase activation by DNA lesions. Instead, the COP9 signalosome (CSN) mediates the CRL4(DDB2) inhibition in a CSN5 independent, nonenzymatic, fashion. In turn, CSN inhibition is relieved upon DNA damage binding to the DDB2 module within CSN-CRL4(DDB2). The Cockayne syndrome A DCAF complex crystal structure shows that CRL4(DCAF(WD40)) ligases share common architectural features. Our data support a general mechanism of ligase activation, which is induced by CSN displacement from CRL4(DCAF) on substrate binding to the DCAF.

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“…Different DNA repair mechanisms remove different lesions and collectively safeguard genome stability. Nucleotide excision repair (NER) is a crucial pathway to detect and eliminate various lesions which mainly include two major lesions-cyclobutane pyrimidine dimers (CPD) and 6-4 pyrimidine-pyrimidone photoproducts (6-4PP) which are induced by UV irradiation [ 60 ]. NER includes two distinct subpathways: global genome NER (GG-NER), which removes lesions in the whole genome DNA, and transcription-coupled NER (TC-NER), which repairs DNA lesions in the transcribed strand of active genes [ 61 ].…”

Section: Crl4 and Nermentioning

confidence: 99%

The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications

2015

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CRLs (Cullin-RING E3 ubiquitin ligases) are the largest E3 ligase family in eukaryotes, which ubiquitinate a wide range of substrates involved in cell cycle regulation, signal transduction, transcriptional regulation, DNA damage response, genomic integrity, tumor suppression and embryonic development. CRL4 E3 ubiquitin ligase, as one member of CRLs family, consists of a RING finger domain protein, cullin4 (CUL4) scaffold protein and DDB1–CUL4 associated substrate receptors. The CUL4 subfamily includes two members, CUL4A and CUL4B, which share extensively sequence identity and functional redundancy. Aberrant expression of CUL4 has been found in a majority of tumors. Given the significance of CUL4 in cancer, understanding its detailed aspects of pathogenesis of human malignancy would have significant value for the treatment of cancer. Here, the work provides an overview to address the role of CRL4 E3 ubiquitin ligase in cancer development and progression, and discuss the possible mechanisms of CRL4 ligase involving in many cellular processes associated with tumor. Finally, we discuss its potential value in cancer therapy.

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Inhibition of Transient Gene Expression in Chinese, Hamster Ovary Cells by Triplet‐sensitized Uv‐b Irradiation of Transfected Dna

Cited by 8 publications

References 32 publications

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

Arabidopsis CRL4 Complexes: Surveying Chromatin States and Gene Expression

The Molecular Basis of CRL4DDB2/CSA Ubiquitin Ligase Architecture, Targeting, and Activation

The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications

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