Dynamic two-stage mechanism of versatile DNA damage recognition by xeroderma pigmentosum group C protein

Clement, Flurina C.; Camenisch, Ulrike; Jia, Fu; Kaczmarek, Nina; Mathieu, Nadine; Naegeli, Hanspeter

doi:10.1016/j.mrfmmm.2009.08.005

Cited by 43 publications

(39 citation statements)

References 78 publications

(109 reference statements)

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“…In GGR, the XPC-Human Homolog of RAD23B protein complex acts together with the XPA-Replication Protein A complex to sense CPDs and 6-4PPs. They may have different affinities for each type of UV damage and might need DDB2 for recruitment to CPD, whereas XPC efficiently recognizes 6-4PPs (4,37). Nevertheless, Emmert et al (38) reported that a truncated XPC protein leads to repair of CPDs but not of 6-4PPs.…”

Section: Discussionmentioning

confidence: 99%

“…XP has a frequency of about one per million in the United States and Europe (1,3). Following lesion recognition by DDB2 (XPE), the XPC protein-in association with Rad23B and centrin-2-senses DNA damage and recruits other NER proteins (4). XP-C cells show proficient transcription-coupled (TC)-NER but defective global genome repair (GGR) of damaged DNA, whereas cells from XP complementation groups A, B, D, F, and G are defective in both pathways (2).…”

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confidence: 99%

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Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons

Kuschal

DiGiovanna

Khan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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About 12% of human genetic disorders involve premature termination codons (PTCs). Aminoglycoside antibiotics have been proposed for restoring full-length proteins by readthrough of PTC. To assess the efficiency of readthrough, we selected homozygous and compound heterozygous skin fibroblasts from xeroderma pigmentosum (XP) patients with different PTCs in the XPC DNA repair gene. XP patients have a nucleotide excision repair defect and a 10,000-fold increased risk of UV-induced skin cancer. In six of eight PTC-containing XP-C cells, treatment with Geneticin and gentamicin resulted in (i) stabilized XPC-mRNA, which would have been degraded by nonsense-mediated decay; (ii) increased expression of XPC protein that localized to UV-damaged sites; (iii) recruitment of XPB and XPD proteins to UV DNA damage sites; and (iv) increased repair of 6-4 photoproducts and cyclobutane pyrimidine dimers. Expression of PTC in a transfected vector revealed that readthrough depends on the PTC sequence and its location within the gene. This sensitive DNA repair assay system demonstrates the complexity of response to PTC readthrough inducers. The efficiency of aminoglycoside-mediated readthrough depends on the type and copy number of PTC, the downstream 4+ nucleotide, and the location within the exon. Treatment with small-molecule nonaminoglycoside compounds (PTC124, BZ16, or RTC14) resulted in similarly increased XPC mRNA expression and photoproduct removal with less toxicity than with the aminoglycosides. Characterizing PTC structure and parameters governing effective PTC readthrough may provide a unique prophylactic therapy for skin cancer prevention in XP-C patients.readthrough compounds | UV radiation

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons

Kuschal

DiGiovanna

Khan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…GG-NER interrogates the whole genome for helical distortions via lesion-sensing complexes, DDB1–DDB2 and XPC–hHR23B–CEN2 [57–59]. UV induces dissociation of CSN (constitutively photomorphogenic-9 (COP9) signalosome) from CUL4A and its translocation to chromatin, thereby activating CRL4 complex [60].…”

Section: Cul4a Plays Important Role In Maintaining Cellular Physiologymentioning

confidence: 99%

CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases

Sharma

Nag

2014

Open Biol.

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The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.

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“…There is some evidence of interplay between PARP1 and CSB during this process [133,134] and treatment with PARP inhibitors delays the repair of UV-induced lesions in a CSB-dependent manner [135]. During global genome NER (GG-NER), helix-distorting lesions and unpaired bases are detected by the Xeroderma pigmentosum complementation group proteins XPC and XPE/ DDB2 [136,137]. PARP1 facilitates recruitment and stability of these proteins, via modulation of the DDB2-associated Cullin-RING E3 ubiquitin ligase activity of [138][139][140].…”

Section: Parp1 and Nucleotide Excision Repair (Ner)mentioning

confidence: 99%

The Role of PARPs in DNA Strand Break Repair

Rulten

Dantzer

Caldecott

2015

Cancer Drug Discovery and Development

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ADP-ribosylation is a post-translational modification in which a target protein becomes modified with monomeric, short chains, or long branching chains of ADP-ribose (ADPR). The process can be carried out by a number of ADP-ribosyltransferases and polymerases (ADP-RTs and PARPs) and the consequences of ribosylation are as diverse and heterogeneous as the products that are formed. In mammalian cells, only three PARPs bind to DNA, and their activity is stimulated by DNA ends. A number of roles for these three PARPs have been characterised, including several functions in DNA repair. The known repertoire of ADPR-binding proteins is vastly expanding, meaning that ribosylation increases the rate and complexity of ways in which DNA is repaired by a number of different ways.

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Dynamic two-stage mechanism of versatile DNA damage recognition by xeroderma pigmentosum group C protein

Cited by 43 publications

References 78 publications

Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons

Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons

CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases

The Role of PARPs in DNA Strand Break Repair

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