scholarly journals Role of Nucleotide Excision Repair in Cisplatin Resistance

2020 ◽  
Vol 21 (23) ◽  
pp. 9248
Author(s):  
Mingrui Duan ◽  
Jenna Ulibarri ◽  
Ke Jian Liu ◽  
Peng Mao
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Resistance Mechanism ◽  
Repair System ◽  
Repair Synthesis ◽  
Wide Range ◽  
Nucleotide Excision ◽  
Damage Mapping

Cisplatin is a chemotherapeutic drug used for the treatment of a number of cancers. The efficacy of cisplatin relies on its binding to DNA and the induction of cytotoxic DNA damage to kill cancer cells. Cisplatin-based therapy is best known for curing testicular cancer; however, treatment of other solid tumors with cisplatin has not been as successful. Pre-clinical and clinical studies have revealed nucleotide excision repair (NER) as a major resistance mechanism against cisplatin in tumor cells. NER is a versatile DNA repair system targeting a wide range of helix-distorting DNA damage. The NER pathway consists of multiple steps, including damage recognition, pre-incision complex assembly, dual incision, and repair synthesis. NER proteins can recognize cisplatin-induced DNA damage and remove the damage from the genome, thereby neutralizing the cytotoxicity of cisplatin and causing drug resistance. Here, we review the molecular mechanism by which NER repairs cisplatin damage, focusing on the recent development of genome-wide cisplatin damage mapping methods. We also discuss how the expression and somatic mutations of key NER genes affect the response of cancer cells to cisplatin. Finally, small molecules targeting NER factors provide important tools to manipulate NER capacity in cancer cells. The status of research on these inhibitors and their implications in cancer treatment will be discussed.

scholarly journals Genetic Characterization of the Nucleotide Excision Repair System of Neisseria gonorrhoeae

2009 ◽  
Vol 192 (3) ◽  
pp. 665-673 ◽  
Author(s):  
Brian E. LeCuyer ◽  
Alison K. Criss ◽  
H. Steven Seifert
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Antigenic Variation ◽  
Excision Repair ◽  
Spontaneous Mutation ◽  
Dna Recombination ◽  
Phase Variation ◽  
Coupling Factor ◽  
Repair System ◽  
Nucleotide Excision

ABSTRACT Nucleotide excision repair (NER) is universally used to recognize and remove many types of DNA damage. In eubacteria, the NER system typically consists of UvrA, UvrB, UvrC, the UvrD helicase, DNA polymerase I, and ligase. In addition, when DNA damage blocks transcription, transcription-repair coupling factor (TRCF), the product of the mfd gene, recruits the Uvr complex to repair the damage. Previous work using selected mutants and assays have indicated that pathogenic Neisseria spp. carry a functional NER system. In order to comprehensively examine the role of NER in Neisseria gonorrhoeae DNA recombination and repair processes, the predicted NER genes (uvrA, uvrB, uvrC, uvrD, and mfd) were each disrupted by a transposon insertion, and the uvrB and uvrD mutants were complemented with a copy of each gene in an ectopic locus. Each uvr mutant strain was highly sensitive to UV irradiation and also showed sensitivity to hydrogen peroxide killing, confirming that all of the NER genes in N. gonorrhoeae are functional. The effect of RecA expression on UV survival was minor in uvr mutants but much larger in the mfd mutant. All of the NER mutants demonstrated wild-type levels of pilin antigenic variation and DNA transformation. However, the uvrD mutant exhibited higher frequencies of PilC-mediated pilus phase variation and spontaneous mutation, a finding consistent with a role for UvrD in mismatch repair. We conclude that NER functions are conserved in N. gonorrhoeae and are important for the DNA repair capabilities of this strict human pathogen.

scholarly journals Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Joseph W. George ◽  
Mika Bessho ◽  
Tadayoshi Bessho
Keyword(s):  
Pancreatic Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Repair Protein ◽  
Nucleotide Excision ◽  
Gemcitabine Treatment ◽  
Nucleotide Excision Repair Protein

Gemcitabine (2′, 2′-difluorodeoxycytidine; dFdC) is a deoxycytidine analog and is used primarily against pancreatic cancer. The cytotoxicity of gemcitabine is due to the inhibition of DNA replication. However, a mechanism of removal of the incorporated dFdC is largely unknown. In this report, we discovered that nucleotide excision repair protein XPF-ERCC1 participates in the repair of gemcitabine-induced DNA damage and inactivation of XPF sensitizes cells to gemcitabine. Further analysis identified that XPF-ERCC1 functions together with apurinic/apyrimidinic endonuclease (APE) in the repair of gemcitabine-induced DNA damage. Our results demonstrate the importance of the evaluation of DNA repair activities in gemcitabine treatment.

scholarly journals Method for assessment of nucleotide excision repair system efficiency ex vivo

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 122-125
Author(s):  
Aleksei A. Popov ◽  
Konstantin E. Orishchenko ◽  
Konstantin N. Naumenko ◽  
Aleksei N. Evdokimov ◽  
Irina O. Petruseva ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Fluorescent Protein ◽  
Excision Repair ◽  
Ex Vivo ◽  
Gene Promoter ◽  
Dna Lesions ◽  
Repair System ◽  
Wide Range ◽  
Nucleotide Excision ◽  
Living Organisms

The nucleotide excision repair (NER) is one of the main repair systems present in the cells of living organisms. It is responsible for the removal of a wide range of bulky DNA lesions. We succeeded in developing a method for assessing the efficiency of NER in the cell (ex vivo), which is a method based on the recovery of TagRFP fluorescent protein production through repair of the damage that blocks the expression of the appropriate gene. Our constructed plasmids containing bulky nFlu or nAnt lesions near the tagrfp gene promoter were shown to undergo repair in eukaryotic cells (HEK 293T) and that they can be used to analyze the efficiency of NER ex vivo. A comparative analysis of the time dependence of fluorescent cells accumulation after transfection with nFlu- and nAnt-DNA revealed that there are differences in how efficient their repair by the NER system of HEK 293T cells can be. The method can be used to assess the cell repair status and the repair efficiency of different structural damages.

scholarly journals The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage

1999 ◽  
Vol 27 (16) ◽  
pp. 3276-3282 ◽  
Author(s):  
P. P. H. Van Sloun ◽  
J. G. Jansen ◽  
G. Weeda ◽  
L. H. F. Mullenders ◽  
A. A. van Zeeland ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Embryonic Stem Cells ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Embryonic Stem ◽  
Genotoxic Effects ◽  
Nucleotide Excision
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