Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy

Xu, Yongfen; Her, Chengtao

doi:10.3390/biom5031652

Cited by 112 publications

(93 citation statements)

References 116 publications

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“…chRFWD3 This is dissimilar to synthetic lethality that affects all cells with deficient HR. Synthetic lethality occurs when there is a potent and lethal synergy between 2 otherwise nonlethal events: in this context, 1 element is camptothecin, a highly specific DNA topoisomerase I inhibitor that acts to maintain single-strand breaks generated by topoisomerases during replication (39), or olaparib, a PARP inhibitor that also blocks repair of DNA single-strand breaks (40). Unrepaired single-strand breaks are converted to doublestrand breaks upon replication.…”

Section: Discussionmentioning

confidence: 99%

Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia

Knies¹,

Inano²,

Ramı́rez³

et al. 2017

Journal of Clinical Investigation

169

171

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The WD40-containing E3 ubiquitin ligase RFWD3 has been recently linked to the repair of DNA damage by homologous recombination (HR). Here we have shown that an RFWD3 mutation within the WD40 domain is connected to the genetic disease Fanconi anemia (FA). An individual presented with congenital abnormalities characteristic of FA. Cells from the patient carrying the compound heterozygous mutations c.205_206dupCC and c.1916T>A in RFWD3 showed increased sensitivity to DNA interstrand cross-linking agents in terms of increased chromosomal breakage, reduced survival, and cell cycle arrest in G 2 phase. The cellular phenotype was mirrored in genetically engineered human and avian cells by inactivation of RFWD3 or introduction of the patient-derived missense mutation, and the phenotype was rescued by expression of wild-type RFWD3 protein. HR was disrupted in RFWD3-mutant cells as a result of impaired relocation of mutant RFWD3 to chromatin and defective physical interaction with replication protein A. Rfwd3 knockout mice appear to have increased embryonic lethality, are subfertile, show ovarian and testicular atrophy, and have a reduced lifespan resembling that of other FA mouse models. Although RFWD3 mutations have thus far been detected in a single child with FA, we propose RFWD3 as an FA gene, FANCW, supported by cellular paradigm systems and an animal model.

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Section: Discussionmentioning

confidence: 99%

Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia

Knies¹,

Inano²,

Ramı́rez³

et al. 2017

Journal of Clinical Investigation

169

171

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“…PIMI has a known function of regulating cell cycle progression from late G1 through S-phase. In addition, STAG2 , TOP1 , and MAD2L2 were also miRNA targets that are involved in cell cycle processes including formation of the cohesion complex which is necessary for the separation of sister chromatids, alterations of topologic states, and accurate mitosis (Li et al, 2015; Listovsky et al, 2013; Xu et al, 2015). One limitation of the targeting analysis is that the samples analyzed in the current study and in the past transcriptomic analysis was from different biological samples.…”

Section: Discussionmentioning

confidence: 99%

Embryonic atrazine exposure alters zebrafish and human miRNAs associated with angiogenesis, cancer, and neurodevelopment

Wirbisky

Weber

Schlotman

et al. 2016

Food and Chemical Toxicology

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MicroRNAs (miRNAs) are short, single-stranded RNA that regulate post-transcriptional control of mRNA translation. Knowledge on the role of these critical regulators in toxicological responses in increasing, but is still limited. Atrazine is a herbicide used throughout the Midwestern US that is reported to frequently contaminate potable water supplies above the maximum contaminant level of 3 parts per billion. Atrazine is a suspected endocrine disrupting chemical and studies have begun to investigate the genetic mechanisms of toxicity; however, studies investigating epigenetic mechanisms are limited. In this study both zebrafish and human miRNAs were significantly altered in response to an embryonic atrazine exposure of 0.3, 3, or 30 ppb in zebrafish. Altered miRNAs are known to play a role in angiogenesis, cancer, or neuronal development, differentiation, and maturation. Targeted analysis of altered human miRNAs with genes previously identified to be altered by atrazine exposure revealed several targets linked to cell cycle and cell signaling. Further analysis of hsa-miRNA-126-3p, which had altered expression in all three atrazine treatments at 72 hpf, revealed alterations also occurred at 60 hpf in the 30 ppb treatment group. Results from this study indicate miRNA deregulation in zebrafish and human miRNAs following an embryonic atrazine exposure in zebrafish.

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“…inhibitors work by blocking the ligation step of the cell cycle by generating single and double strands breaks which in turn harm the integrity of the genome; the break results to apoptosis cell death [24]. Apparently, TOP1 inhibitors play a great role towards cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes

Shadrack¹,

Ndesendo²

2017

CMB

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Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, Cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.

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Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy

Cited by 112 publications

References 116 publications

Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia

Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia

Embryonic atrazine exposure alters zebrafish and human miRNAs associated with angiogenesis, cancer, and neurodevelopment

Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes

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