Journal ArticleDOI
Induction of sister chromatid exchange by 3-aminobenzamide is independent of bromodeoxyuridine
W.F. Morgan,S. Wolff +1 more
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SCE induction by 3AB in the second cycle is not dependent on the presence of BrdU in template DNA, suggesting that an imbalance in the deoxycytidine precursor pool did not account for the effect.Abstract:
The poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3AB), significantly increases sister chromatid exchange (SCE) frequency without causing apparent damage to cellular DNA. A previous study has suggested that the increase of SCEs by 3AB results from DNA replication on a template strand containing bromodeoxyuridine (BrdU), which is used to visualize SCEs. Therefore, to study the importance of BrdU incorporation on the induction of SCEs by 3AB, we analyzed exchanges induced during the first round of replication (twin SCEs) and those induced during the second (single SCEs). 3AB increased the formation of SCEs in both replication cycles, but significantly more exchanges were induced in the second cycle, when BrdU was present in the template DNA. These data are consistent with the suggestion that the presence of BrdU in the template strand of DNA plays an important role in SCE induction by 3AB. However, we also studied 3AB-induced SCEs by autoradiography of cells cultured with 3H-thymidine (3H-dT) instead of BrdU. A significant increase in SCE frequency was also observed in cells from these cultures. Furthermore, the analysis of twin and single SCEs showed that with 3H-dT too, there was a greater increase in SCEs in the second cycle than in the first. Thus, SCE induction by 3AB in the second cycle is not dependent on the presence of BrdU in template DNA. Incubation of cells with deoxycytidine was found to have no effect on the frequency of SCEs induced by 3AB, suggesting that an imbalance in the deoxycytidine precursor pool did not account for the effect.read more
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Journal ArticleDOI
Poly(adp-ribosyl)ation reactions in the regulation of nuclear functions
TL;DR: The total dependence of poly(ADP-ribose) synthesis on DNA strand breaks strongly suggests that this post-translational modification is involved in the metabolism of nucleic acids, and the presence of PARP in these multiprotein complexes clearly supports an important role for poly(ADE-ribosyl)ation reactions in DNA transactions.
Journal ArticleDOI
Poly(ADP-ribose)polymerase: a perplexing participant in cellular responses to DNA breakage
TL;DR: The polymerization cycle consequently is a major player in the response of cells to DNA breakage, but the game it plays is yet to be explained.
Journal ArticleDOI
The genetic toxicology of 5-bromodeoxyuridine in mammalian cells
TL;DR: Experimental evidence clearly supports the contention that Brd Urd exerts its effects on eukaryotic cells through mechanisms similar to those originally proposed to explain the genotoxicity of BrdUrd.
Book ChapterDOI
Poly(ADP-ribose) polymerase: A guardian of the genome that facilitates DNA repair by protecting against DNA recombination
TL;DR: It is proposed that PARP is a guardian of the genome that protects against DNA recombination and creates a dilemma as to how PARP can be involved in DNA repair in only selected growth phases while it is functionally active in all growth phases.
Journal ArticleDOI
Strand breaks arising from the repair of the 5-bromodeoxyuridine-substituted template and methyl methanesulphonate-induced lesions can explain the formation of sister chromatid exchanges
Roy Saffhill,Charles H Ockey +1 more
TL;DR: A model for Sce induction is proposed involving a single-strand break or gap as the initial requirement for SCE initiation at the replicating fork, resulting in enhanced SCE levels during the second cycle of BrdU incorporation.