scholarly journals Polynuclear ruthenium organometallic compounds induce DNA damage in human cells identified by the nucleotide excision repair factor XPC

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Olivia G. Fast ◽  
Brittany Gentry ◽  
Liah Strouth ◽  
Madison B. Niece ◽  
Floyd A. Beckford ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Organometallic Compounds ◽  
Chemotherapeutic Agents ◽  
Human Cells ◽  
Nucleotide Excision ◽  
Antibiotic Efficacy ◽  
In Cells

Abstract Ruthenium organometallic compounds represent an attractive avenue in developing alternatives to platinum-based chemotherapeutic agents. While evidence has been presented indicating ruthenium-based compounds interact with isolated DNA in vitro, it is unclear what effect these compounds exert in cells. Moreover, the antibiotic efficacy of polynuclear ruthenium organometallic compounds remains uncertain. In the present study, we report that exposure to polynuclear ruthenium organometallic compounds induces recruitment of damaged DNA sensing protein Xeroderma pigmentosum Group C into chromatin-immobilized foci. Additionally, we observed one of the tested polynuclear ruthenium organometallic compounds displayed increased cytotoxicity against human cells deficient in nucleotide excision repair (NER). Taken together, these results suggest that polynuclear ruthenium organometallic compounds induce DNA damage in cells, and that cellular resistance to these compounds may be influenced by the NER DNA repair phenotype of the cells.

scholarly journals Nucleotide Excision Repair in Human Cells

2013 ◽  
Vol 288 (29) ◽  
pp. 20918-20926 ◽  
Author(s):  
Jinchuan Hu ◽  
Jun-Hyuk Choi ◽  
Shobhan Gaddameedhi ◽  
Michael G. Kemp ◽  
Joyce T. Reardon ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Genomic Dna ◽  
Excision Repair ◽  
Human Cells ◽  
Naked Dna ◽  
Nucleotide Excision ◽  
Uv Photoproducts ◽  
Mutant Cells

Nucleotide excision repair is the sole mechanism for removing the major UV photoproducts from genomic DNA in human cells. In vitro with human cell-free extract or purified excision repair factors, the damage is removed from naked DNA or nucleosomes in the form of 24- to 32-nucleotide-long oligomers (nominal 30-mer) by dual incisions. Whether the DNA damage is removed from chromatin in vivo in a similar manner and what the fate of the excised oligomer was has not been known previously. Here, we demonstrate that dual incisions occur in vivo identical to the in vitro reaction. Further, we show that transcription-coupled repair, which operates in the absence of the XPC protein, also generates the nominal 30-mer in UV-irradiated XP-C mutant cells. Finally, we report that the excised 30-mer is released from the chromatin in complex with the repair factors TFIIH and XPG. Taken together, our results show the congruence of in vivo and in vitro data on nucleotide excision repair in humans.

O V A.1 Nucleotide excision repair mechanism in human cells: Analysis by in vitro assays

1997 ◽  
Vol 379 (1) ◽  
pp. S33
Author(s):  
Bernard Salles ◽  
Patrick Calsou ◽  
Philippe Frit ◽  
Ruo-Ya Li ◽  
Catherine Muller ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Human Cells ◽  
In Vitro Assays ◽  
Repair Mechanism ◽  
Nucleotide Excision

scholarly journals UvrD Participation in Nucleotide Excision Repair Is Required for the Recovery of DNA Synthesis following UV-Induced Damage inEscherichia coli

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kelley N. Newton ◽  
Charmain T. Courcelle ◽  
Justin Courcelle
Keyword(s):  
Dna Damage ◽  
Dna Synthesis ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Dna Helicase ◽  
Replication Forks ◽  
Nucleotide Excision ◽  
Fork Regression

UvrD is a DNA helicase that participates in nucleotide excision repair and several replication-associated processes, including methyl-directed mismatch repair and recombination. UvrD is capable of displacing oligonucleotides from synthetic forked DNA structuresin vitroand is essential for viability in the absence of Rep, a helicase associated with processing replication forks. These observations have led others to propose that UvrD may promote fork regression and facilitate resetting of the replication fork following arrest. However, the molecular activity of UvrD at replication forksin vivohas not been directly examined. In this study, we characterized the role UvrD has in processing and restoring replication forks following arrest by UV-induced DNA damage. We show that UvrD is required for DNA synthesis to recover. However, in the absence of UvrD, the displacement and partial degradation of the nascent DNA at the arrested fork occur normally. In addition, damage-induced replication intermediates persist and accumulate inuvrDmutants in a manner that is similar to that observed in other nucleotide excision repair mutants. These data indicate that, following arrest by DNA damage, UvrD is not required to catalyze fork regressionin vivoand suggest that the failure ofuvrDmutants to restore DNA synthesis following UV-induced arrest relates to its role in nucleotide excision repair.

scholarly journals UV radiation-induced SUMOylation of DDB2 regulates nucleotide excision repair

2017 ◽  
Vol 38 (10) ◽  
pp. 976-985 ◽  
Author(s):  
Chunhua Han ◽  
Ran Zhao ◽  
John Kroger ◽  
Jinshan He ◽  
Gulzar Wani ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Uv Radiation ◽  
Uv Irradiation ◽  
Excision Repair ◽  
26S Proteasome ◽  
Cell Extracts ◽  
Nucleotide Excision

Abstract Subunit 2 of DNA damage-binding protein complex (DDB2) is an early sensor of nucleotide excision repair (NER) pathway for eliminating DNA damage induced by UV radiation (UVR) and cisplatin treatments of mammalian cells. DDB2 is modified by ubiquitin and poly(ADP-ribose) (PAR) in response to UVR, and these modifications play a crucial role in regulating NER. Here, using immuno-analysis of irradiated cell extracts, we have identified multiple post-irradiation modifications of DDB2 protein. Interestingly, although the DNA lesions induced by both UVR and cisplatin are corrected by NER, only the UV irradiation, but not the cisplatin treatment, induces any discernable DDB2 modifications. We, for the first time, show that the appearance of UVR-induced DDB2 modifications depend on the binding of DDB2 to the damaged chromatin and the participation of functionally active 26S proteasome. The in vitro and in vivo analysis revealed that SUMO-1 conjugations comprise a significant portion of these UVR-induced DDB2 modifications. Mapping of SUMO-modified sites demonstrated that UVR-induced SUMOylation occurs on Lys-309 residue of DDB2 protein. Mutation of Lys-309 to Arg-309 diminished the DDB2 SUMOylation observable both in vitro and in vivo. Moreover, K309R mutated DDB2 lost its function of recruiting XPC to the DNA damage sites, as well as the ability to repair cyclobutane pyrimidine dimers following cellular UV irradiation. Taken together, our results indicate that DDB2 is modified by SUMOylation upon UV irradiation, and this post-translational modification plays an important role in the initial recognition and processing of UVR-induced DNA damage occurring within the context of chromatin.

scholarly journals Human cells deficient in p53 regulated p21waf1/cip1 expression exhibit normal nucleotide excision repair of UV-induced DNA damage

2002 ◽  
Vol 23 (3) ◽  
pp. 403-410 ◽  
Author(s):  
Manzoor A. Wani ◽  
Gulzar Wani ◽  
Jihonag Yao ◽  
Qianzheng Zhu ◽  
Altaf A. Wani
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Human Cells ◽  
Nucleotide Excision

scholarly journals Nucleotide Excision Repair in Caenorhabditis elegans

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Hannes Lans ◽  
Wim Vermeulen
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Current Knowledge ◽  
Uv Light ◽  
Molecular Model ◽  
Model Systems ◽  
C Elegans ◽  
Nucleotide Excision

Nucleotide excision repair (NER) plays an essential role in many organisms across life domains to preserve and faithfully transmit DNA to the next generation. In humans, NER is essential to prevent DNA damage-induced mutation accumulation and cell death leading to cancer and aging. NER is a versatile DNA repair pathway that repairs many types of DNA damage which distort the DNA helix, such as those induced by solar UV light. A detailed molecular model of the NER pathway has emerged from in vitro and live cell experiments, particularly using model systems such as bacteria, yeast, and mammalian cell cultures. In recent years, the versatility of the nematode C. elegans to study DNA damage response (DDR) mechanisms including NER has become increasingly clear. In particular, C. elegans seems to be a convenient tool to study NER during the UV response in vivo, to analyze this process in the context of a developing and multicellular organism, and to perform genetic screening. Here, we will discuss current knowledge gained from the use of C. elegans to study NER and the response to UV-induced DNA damage.

scholarly journals UV Light-induced DNA Damage and Tolerance for the Survival of Nucleotide Excision Repair-deficient Human Cells

2004 ◽  
Vol 279 (45) ◽  
pp. 46674-46677 ◽  
Author(s):  
Satoshi Nakajima ◽  
Li Lan ◽  
Shin-ichiro Kanno ◽  
Masashi Takao ◽  
Kazuo Yamamoto ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Human Cells ◽  
Nucleotide Excision
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