The Involvement of Topoisomerase I in the Induction of DNA-Protein Crosslinks and DNA Single-Strand Breaks in Cells of Ultraviolet-Irradiated Human and Frog Cell Lines

1997 ◽  
Vol 148 (6) ◽  
pp. 575 ◽  
Author(s):  
Barry S. Rosenstein ◽  
Deepa Subramanian ◽  
Mark T. Muller
Keyword(s):  
Cell Lines ◽  
Topoisomerase I ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Protein Crosslinks ◽  
In Cells

REPAIR OF NEAR-VISIBLE- and BLUE-LIGHT-INDUCED DNA SINGLE-STRAND BREAKS BY THE CHO CELL LINES AA8 and EM9

1991 ◽  
Vol 54 (4) ◽  
pp. 639-644 ◽  
Author(s):  
Mark E. Churchill ◽  
Jennifer G. Peak ◽  
Meyrick J. Peak
Keyword(s):  
Blue Light ◽  
Cell Lines ◽  
Single Strand ◽  
Cho Cell ◽  
Strand Breaks ◽  
Single Strand Breaks

Causes of DNA single-strand breaks during reduction of chromate by glutathione in vitro and in cells

2006 ◽  
Vol 40 (11) ◽  
pp. 1981-1992 ◽  
Author(s):  
Joseph Messer ◽  
Mindy Reynolds ◽  
Lauren Stoddard ◽  
Anatoly Zhitkovich
Keyword(s):  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
In Cells

scholarly journals Spontaneous Homologous Recombination Is Induced by Collapsed Replication Forks That Are Caused by Endogenous DNA Single-Strand Breaks

2005 ◽  
Vol 25 (16) ◽  
pp. 7158-7169 ◽  
Author(s):  
Nasrollah Saleh-Gohari ◽  
Helen E. Bryant ◽  
Niklas Schultz ◽  
Kayan M. Parker ◽  
Tobias N. Cassel ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Cell Line ◽  
Mammalian Cells ◽  
Topoisomerase I ◽  
Fibroblast Cell ◽  
Single Strand ◽  
Replication Forks ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Recombination Repair

ABSTRACT Homologous recombination is vital to repair fatal DNA damage during DNA replication. However, very little is known about the substrates or repair pathways for homologous recombination in mammalian cells. Here, we have compared the recombination products produced spontaneously with those produced following induction of DNA double-strand breaks (DSBs) with the I-SceI restriction endonuclease or after stalling or collapsing replication forks following treatment with thymidine or camptothecin, respectively. We show that each lesion produces different spectra of recombinants, suggesting differential use of homologous recombination pathways in repair of these lesions. The spontaneous spectrum most resembled the spectra produced at collapsed replication forks formed when a replication fork runs into camptothecin-stabilized DNA single-strand breaks (SSBs) within the topoisomerase I cleavage complex. We found that camptothecin-induced DSBs and the resulting recombination repair require replication, showing that a collapsed fork is the substrate for camptothecin-induced recombination. An SSB repair-defective cell line, EM9 with an XRCC1 mutation, has an increased number of spontaneous γH2Ax and RAD51 foci, suggesting that endogenous SSBs collapse replication forks, triggering recombination repair. Furthermore, we show that γH2Ax, DSBs, and RAD51 foci are synergistically induced in EM9 cells with camptothecin, suggesting that lack of SSB repair in EM9 causes more collapsed forks and more recombination repair. Furthermore, our results suggest that two-ended DSBs are rare substrates for spontaneous homologous recombination in a mammalian fibroblast cell line. Interestingly, all spectra showed evidence of multiple homologous recombination events in 8 to 16% of clones. However, there was no increase in homologous recombination genomewide in these clones nor were the events dependent on each other; rather, we suggest that a first homologous recombination event frequently triggers a second event at the same locus in mammalian cells.

scholarly journals Deoxyguanosine enhances the cytotoxicity of the topoisomerase I inhibitor camptothecin by reducing the repair of double-strand breaks induced in replicating DNA

1991 ◽  
Vol 100 (4) ◽  
pp. 883-893 ◽  
Author(s):  
S. Squires ◽  
A.J. Ryan ◽  
H.L. Strutt ◽  
P.J. Smith ◽  
R.T. Johnson
Keyword(s):  
Topoisomerase I ◽  
S Phase ◽  
Double Strand Breaks ◽  
Single Strand ◽  
Pulse Field ◽  
Dependent Manner ◽  
Chromosomal Dna ◽  
Dna Breaks ◽  
Strand Breaks ◽  
Single Strand Breaks

Deoxyguanosine (dG) enhances the S phase cytotoxicity of camptothecin (CPT), a topoisomerase I (topo I) inhibitor, but by contrast does not affect the toxicity of VM26, a topoisomerase II inhibitor. The 80% survival of S phase human fibroblasts after a 60 min exposure to 0.2 microM CPT is reduced by half in the presence of 25 microM dG. G1 cells are resistant to CPT toxicity, though the levels of the single-strand DNA breaks induced by the drug are similar in G1 and S phase cells. Higher concentrations of dG retard the recovery of RNA and DNA synthesis and inhibit recovery from the S-G2 cycle block after CPT removal. At 100 microM dG the number of CPT-induced protein-linked single-strand DNA breaks is almost doubled, suggestive of a direct effect of dG on the cellular activity of topo I. In the presence or absence of dG, single-strand breaks disappear within minutes of the removal of CPT. We found that the inhibition of topo I by CPT induces the formation of double as well as single-strand breaks in the chromosomal DNA. Previously we have shown, using a pulse-field gel electrophoresis technique, that the double-strand breaks (DSBs) are generated predominantly at sites of replication and not in the bulk DNA. A number of these DSBs are long-lived. The present study shows that dG affects the repair of these DSBs in a dose-dependent manner, and that a higher proportion of the initial lesions induced in nascent DNA remain 24 h after removal of CPT. We suggest that the long-lived double-strand breaks, formed in replicating DNA at the time of CPT exposure, are the lethal drug-induced lesions, which explains both the selective cytotoxicity of CPT towards S phase cells and the enhancement of CPT cytotoxicity by dG.

DNA Single Strand Breaks Induced by Low Levels of Occupational Exposure to Styrene: The Gap between Standards and Reality

2002 ◽  
Vol 21 (1) ◽  
pp. 5 ◽  
Author(s):  
Magdy Y. Shamy ◽  
Hazem H. Osman ◽  
Kamal M. Kandeel ◽  
Nehad M. Abdel-Moneim ◽  
Khalid F. El Said
Keyword(s):  
Occupational Exposure ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Low Levels
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