Differential sensitivity of histone acetylation in nitrogen-mustard sensitive and resistant cells. Relation to drug uptake, formation and repair of DNA-interstrand cross-links

1988 ◽  
Vol 24 (12) ◽  
pp. 1861-1868 ◽  
Author(s):  
Wilfried Helliger ◽  
Johann Hofmann ◽  
Karl Maly ◽  
Wolfgang Doppler ◽  
Bernd-Jochen Hermann ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Nitrogen Mustard ◽  
Drug Uptake ◽  
Differential Sensitivity ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Resistant Cells

scholarly journals Cho Endonuclease Functions during DNA Interstrand Cross-Link Repair in Escherichia coli

2016 ◽  
Vol 198 (22) ◽  
pp. 3099-3108 ◽  
Author(s):  
Anthonige Vidya Perera ◽  
James Brian Mendenhall ◽  
Charmain Tan Courcelle ◽  
Justin Courcelle
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Repair Process ◽  
Differential Sensitivity ◽  
Duplex Dna ◽  
Dna Lesion ◽  
Nucleotide Excision ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Complex Lesions

ABSTRACTDNA interstrand cross-links are complex lesions that covalently link both strands of the duplex DNA. Lesion removal is proposed to be initiated via the UvrABC nucleotide excision repair complex; however, less is known about the subsequent steps of this complex repair pathway. In this study, we characterized the contribution of nucleotide excision repair mutants to survival in the presence of psoralen-induced damage. Unexpectedly, we observed that the nucleotide excision repair mutants exhibit differential sensitivity to psoralen-induced damage, withuvrCmutants being less sensitive than eitheruvrAoruvrB. We show that Cho, an alternative endonuclease, acts with UvrAB and is responsible for the reduced hypersensitivity ofuvrCmutants. We find that Cho's contribution to survival correlates with the presence of DNA interstrand cross-links, rather than monoadducts, and operates at a step after, or independently from, the initial incision during the global repair of psoralen DNA adducts from the genome.IMPORTANCEDNA interstrand cross-links are complex lesions that covalently bind to both strands of the duplex DNA and whose mechanism of repair remains poorly understood. In this study, we show that Cho, an alternative endonuclease, acts with UvrAB and participates in the repair of DNA interstrand cross-links formed in the presence of photoactivated psoralens. Cho's contribution to survival correlates with the presence of DNA interstrand cross-links and operates at a step after, or independently from, the initial incision during the repair process.

scholarly journals DNA Polymerase II (polB) Is Involved in a New DNA Repair Pathway for DNA Interstrand Cross-Links inEscherichia coli

1999 ◽  
Vol 181 (9) ◽  
pp. 2878-2882 ◽  
Author(s):  
Mark Berardini ◽  
Patricia L. Foster ◽  
Edward L. Loechler
Keyword(s):  
Dna Polymerase ◽  
Nitrogen Mustard ◽  
Wild Type ◽  
Cross Link ◽  
Replication Efficiency ◽  
E Coli ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
The Cross ◽  
Dna Polymerase Ii

ABSTRACT DNA-DNA interstrand cross-links are the cytotoxic lesions for many chemotherapeutic agents. A plasmid with a single nitrogen mustard (HN2) interstrand cross-link (inter-HN2-pTZSV28) was constructed and transformed into Escherichia coli, and its replication efficiency (RE = [number of transformants from inter-HN2-pTZSV28]/[number of transformants from control]) was determined to be ∼0.6. Previous work showed that RE was high because the cross-link was repaired by a pathway involving nucleotide excision repair (NER) but not recombination. (In fact, recombination was precluded because the cells do not receive lesion-free homologous DNA.) Herein, DNA polymerase II is shown to be in this new pathway, since the replication efficiency (RE) is higher in apolB + (∼0.6) than in a ΔpolB(∼0.1) strain. Complementation with apolB +-containing plasmid restores RE to wild-type levels, which corroborates this conclusion. In separate experiments, E. coli was treated with HN2, and the relative sensitivity to killing was found to be as follows: wild type <polB < recA < polB recA ∼ uvrA. Because cells deficient in either recombination (recA) or DNA polymerase II (polB) are hypersensitive to nitrogen mustard killing,E. coli appears to have two pathways for cross-link repair: an NER/recombination pathway (which is possible when the cross-links are formed in cells where recombination can occur because there are multiple copies of the genome) and an NER/DNA polymerase II pathway. Furthermore, these results show that some cross-links are uniquely repaired by each pathway. This represents one of the first clearly defined pathway in which DNA polymerase II plays a role in E. coli. It remains to be determined why this new pathway prefers DNA polymerase II and why there are two pathways to repair cross-links.

Electron microscopic study of the membrane glycoproteins in the rat kidney after cisplatin treatment

1989 ◽  
Vol 47 ◽  
pp. 912-913
Author(s):  
S.K. Aggarwal
Keyword(s):  
Alkaline Phosphatase ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Kidney Tissue ◽  
Membrane Glycoproteins ◽  
Electron Microscopic ◽  
Before And After ◽  
Interstrand Cross Links ◽  
Cross Links

The proposed primary mechanism of action of the anticancer drug cisplatin (Cis-DDP) is through its interaction with DNA, mostly through DNA intrastrand cross-links or DNA interstrand cross-links. DNA repair mechanisms can circumvent this arrest thus permitting replication and transcription to proceed. Various membrane transport enzymes have also been demonstrated to be effected by cisplatin. Glycoprotein alkaline phosphatase was looked at in the proximal tubule cells before and after cisplatin both in vivo and in vitro for its inactivation or its removal from the membrane using light and electron microscopy.Outbred male Swiss Webster (Crl: (WI) BR) rats weighing 150-250g were given ip injections of cisplatin (7mg/kg). Animals were killed on day 3 and day 5. Thick slices (20-50.um) of kidney tissue from treated and untreated animals were fixed in 1% buffered glutaraldehyde and 1% formaldehyde (0.05 M cacodylate buffer, pH 7.3) for 30 min at 4°C. Alkaline phosphatase activity and carbohydrates were demonstrated according to methods described earlier.

Increased gene-specific repair of cisplatin interstrand cross-links in cisplatin-resistant human ovarian cancer cell lines

1992 ◽  
Vol 12 (9) ◽  
pp. 3689-3698
Author(s):  
W Zhen ◽  
C J Link ◽  
P M O'Connor ◽  
E Reed ◽  
R Parker ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ovarian Cancer Cell ◽  
Parental Cell ◽  
Resistant Cell ◽  
Dhfr Gene ◽  
Human Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Lines ◽  
Repair Efficiency ◽  
Interstrand Cross Links ◽  
Cross Links

We have studied several aspects of DNA damage formation and repair in human ovarian cancer cell lines which have become resistant to cisplatin through continued exposure to the anticancer drug. The resistant cell lines A2780/cp70 and 2008/c13*5.25 were compared with their respective parental cell lines, A2780 and 2008. Cells in culture were treated with cisplatin, and the two main DNA lesions formed, intrastrand adducts and interstrand cross-links, were quantitated before and after repair incubation. This quantitation was done for total genomic lesions and at the level of individual genes. In the overall genome, the initial frequency of both cisplatin lesions assayed was higher in the parental than in the derivative resistant cell lines. Nonetheless, the total genomic repair of each of these lesions was not increased in the resistant cells. These differences in initial lesion frequency between parental and resistant cell lines were not observed at the gene level. Resistant and parental cells had similar initial frequencies of intrastrand adducts and interstrand cross-links in the dihydrofolate reductase (DHFR) gene and in several other genes after cisplatin treatment of the cells. There was no increase in the repair efficiency of intrastrand adducts in the DHFR gene in resistant cell lines compared with the parental partners. However, a marked and consistent repair difference between parental and resistant cells was observed for the gene-specific repair of cisplatin interstrand cross-links. DNA interstrand cross-links were removed from three genes, the DHFR, multidrug resistance (MDR1), and delta-globin genes, much more efficiently in the resistant cell lines than in the parental cell lines. Our findings suggest that acquired cellular resistance to cisplatin may be associated with increased gene-specific DNA repair efficiency of a specific lesion, the interstrand cross-link.

scholarly journals The Pso4 mRNA Splicing and DNA Repair Complex Interacts with WRN for Processing of DNA Interstrand Cross-links

2005 ◽  
Vol 280 (49) ◽  
pp. 40559-40567 ◽  
Author(s):  
Nianxiang Zhang ◽  
Ramandeep Kaur ◽  
Xiaoyan Lu ◽  
Xi Shen ◽  
Lei Li ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mrna Splicing ◽  
Interstrand Cross Links ◽  
Cross Links
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