The Topoisomerase-related Function Gene TRF4 Affects Cellular Sensitivity to the Antitumor Agent Camptothecin

Walowsky, Carrie; Fitzhugh, David J.; Castaño, Irene; Ju, Justina Y.; Levin, Nikki A.; Christman, Michael F.

doi:10.1074/jbc.274.11.7302

Cited by 66 publications

(52 citation statements)

References 33 publications

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“…Plates were incubated at 301C for 2 days. 33 The genetic descriptions of the yeast strains are as follows Measurement of mitochondrial membrane potential. Mitochondrial transmembrane potential was investigated using JC1 dye.…”

Section: Methodsmentioning

confidence: 99%

Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I–DNA complex

et al. 2006

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Protein kinase C (PKC) is an important constituent of the signaling pathways involved in apoptosis. We report here that like staurosporine, withaferin A is a potent inhibitor of PKC. In Leishmania donovani, the inhibition of PKC by withaferin A causes depolarization of DW m and generates ROS inside cells. Loss of DW m leads to the release of cytochrome c into the cytosol and subsequently activates caspase-like proteases and oligonucleosomal DNA cleavage. Moreover, in treated cells, oxidative DNA lesions facilitate the stabilization of topoisomerase I-mediated cleavable complexes, which also contribute to DNA fragmentation. However, withaferin A and staurosporine cannot induce cleavable complex formation in vitro with recombinant topoisomerase I nor with nuclear extracts from control cells. Taken together, our results indicate that inhibition of PKC by withaferin A is a central event for the induction of apoptosis and that the stabilization of topoisomerase I-DNA complex is necessary to amplify apoptotic process.

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Section: Methodsmentioning

confidence: 99%

Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I–DNA complex

et al. 2006

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“…Another prediction is that mutants defective in sister chromatid cohesion should be defective in replication fork repair. Interestingly, trf4 and mcd1 yeast mutants, defective in sister chromatid cohesion, are exquisitely sensitive to camptothecin and to methyl methanesulfonate [the agents that are thought to cause replication fork collapse (109, 110)] but are not sensitive to UV (111).…”

Section: Enzymology Of the Yeast Recombination: Rad54-promoted Duplexmentioning

confidence: 99%

DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination

Kuzminov

2001

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

198

126

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Proceedings of the National Academy of Sciences Colloquium on the roles of homologous recombination in DNA replication are summarized. Current findings in experimental systems ranging from bacteriophages to mammalian cell lines substantiate the idea that homologous recombination is a system supporting DNA replication when either the template DNA is damaged or the replication machinery malfunctions. There are several lines of supporting evidence: (i) DNA replication aggravates preexisting DNA damage, which then blocks subsequent replication; (ii) replication forks abandoned by malfunctioning replisomes become prone to breakage; (iii) mutants with malfunctioning replisomes or with elevated levels of DNA damage depend on homologous recombination; and (iv) homologous recombination primes DNA replication in vivo and can restore replication fork structures in vitro. The mechanisms of recombinational repair in bacteriophage T4, Escherichia coli, and Saccharomyces cerevisiae are compared. In vitro properties of the eukaryotic recombinases suggest a bigger role for single-strand annealing in the eukaryotic recombinational repair.

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“…9,15 POLS (Table 2) encodes for a polymerase necessary for several events in DNA metabolism such as chromosome segregation and DNA repair. 12,13 Five genes coding for not characterized proteins (I -V) have not been investigated. Three genes MGC5309, FLJ20303 and the UBC-E2 homolog, FLJ25076, may be candidate genes for the phenotype changes, and have been chosen to be tested on 11 different embryo tissues.…”

Section: Surveying Several Candidate Genesmentioning

confidence: 99%

“…The polymerase has DNA-binding activity, and is involved in DNA replication and chromosome cycle. 12,13 The protein contains a nucleotidyltransferase domain and a PAP/25A-associated domain, which is described as topoisomerase 1 related. 11 MGC5309 is homologous with the Drosophila gene CG5057, and therefore probably codes for a transcriptional coactivator that is a subunit of SRB subcomplex of RNA polymerase II.…”

Section: Biological Materialsmentioning

confidence: 99%

Determination of the ‘critical region’ for cat-like cry of Cri-du-chat syndrome and analysis of candidate genes by quantitative PCR

Niebuhr

Yang

et al. 2005

Eur J Hum Genet

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Cri-du-chat (CDC, OMIM 123450) is a chromosomal syndrome that results from partial deletions on the short arm of chromosome 5. The clinical features of CDC normally include high-pitched cat-like cry, mental retardation, microcephaly, hypertelorism and epicanthic folds. The cat-like cry is the most prominent clinical characteristic in newborn children and is usually considered as diagnostic for the CDC syndrome. Using a strategy of 'phenotype dissection', the critical region for cat-like cry was mapped to the chromosomal segment 5p15.3 -5p15.2 in previous reports. In this study, the distal breakpoints of two interstitial deletions in two clinical distinctive CDC patients are analysed, one with and one without the catlike cry. Using PCR, the critical region for the cat-like cry is mapped to a short 640 kbp region on chromosome 5p. Genome analysis of this critical region reveals a gene-rich sequence containing five known genes, five putative genes and three spliced EST sequences, altogether 71 predicted exons. Three genes, FLJ25076, a homolog to a ubiquitin-conjugating enzyme UBC-E2, FLJ20303, a nucleolar protein NOP2, which may play a role in the regulation of the cell cycle and MGC5309, a protein with similarity to Nut2, a Drosophila transcriptional coactivator, have been characterized and expression profiles determined by quantitative PCR. These results suggest that one candidate gene, FLJ25076, encodes a ubiquitinconjugated enzyme E2 type, which is locally expressed in thoracic and scalp tissues. The other two genes are expressed uniformly in all tissues tested, which suggest that they are housekeeping genes.

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The Topoisomerase-related Function Gene TRF4 Affects Cellular Sensitivity to the Antitumor Agent Camptothecin

Cited by 66 publications

References 33 publications

Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I–DNA complex

Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I–DNA complex

DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination

Determination of the ‘critical region’ for cat-like cry of Cri-du-chat syndrome and analysis of candidate genes by quantitative PCR

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