Size and transforming activity of deoxyribonucleic acid in Diplococcus pneumoniae during thymidine starvation

Bousque, J L; Sicard, N

doi:10.1128/jb.128.2.540-548.1976

Cited by 9 publications

(2 citation statements)

References 26 publications

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“…While numerous studies report accumulation of single-strand breaks in the chromosomal DNA during T-starvation (Freifelder 1969, Walker 1970, Bhattacharjee and Das 1973, Hill and Fangman 1973, Bousque and Sicard 1976, only three studies explicitly addressed the possibility of formation of long single-strand gaps. First, Nakayama and colleagues mentioned a significant single-stranded character of their non-migrating DNA without presenting experimental data (Nakayama, Kusano et al 1994).…”

Section: Accumulation Of Ssdna During T-starvationmentioning

confidence: 99%

Sources of thymidine and analogs fueling futile damage-repair cycles and ss-gap accumulation during thymine starvation in Escherichia coli

Rao

Kuzminov

2019

DNA Repair

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Thymine deprivation in thyA mutant E. coli causes thymineless death (TLD) and is the mode of action of popular antibacterial and anticancer drugs, yet the mechanisms of TLD are still unclear. TLD comprises three defined phases: resistance, rapid exponential death (RED) and survival, with the nature of the resistance phase and of the transition to the RED phase holding key to TLD pathology. We propose that a limited source of endogenous thymine maintains replication forks through the resistance phase. When this source ends, forks undergo futile break-repair cycle during the RED phase, eventually rendering the chromosome non-functional. Two obvious sources of the endogenous thymine are degradation of broken chromosomal DNA and recruitment of thymine from stable RNA. However, mutants that cannot degrade broken chromosomal DNA or lack ribothymine, instead of shortening the resistance phase, deepen the RED phase, meaning that only a small fraction of T-starved cells tap into these sources. Interestingly, the substantial chromosomal DNA accumulation during the resistance phase is negated during the RED phase, suggesting futile cycle of incorporation and excision of wrong nucleotides. We tested incorporation of dU or rU, finding some evidence for both, but DNA-dU incorporation accelerates TLD only when intracellular [dUTP] is increased by the dut mutation. In the dut ung mutant, with increased DNA-dU incorporation and no DNA-dU excision, replication is in fact rescued even without dT, but TLD still occurs, suggesting different mechanisms. Finally, we found that continuous DNA synthesis during thymine starvation makes chromosomal DNA increasingly single-stranded, and even the dut ung defect does not completely block this ss-gap accumulation. We propose that instability of single-strand gaps underlies the pathology of thymine starvation.

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Section: Accumulation Of Ssdna During T-starvationmentioning

confidence: 99%

Sources of thymidine and analogs fueling futile damage-repair cycles and ss-gap accumulation during thymine starvation in Escherichia coli

Rao

Kuzminov

2019

DNA Repair

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“…These alterations are probably not just singlestrand breaks, at least in pneumococcus (3), and they do not occur only at the replication fork (3). They might induce structural changes in the DNA from starved cells, such as incorporation of uracil similar to deoxyuridine triphosphatase-deficient mutants (20) and/or loss of DNAthymine (5).…”

Section: Figmentioning

confidence: 99%

Thymineless death in Escherichia coli dnaB mutants and in a dnaB dnaG double mutant

Sicard¹,

Bouvier²

1977

J Bacteriol

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The interference of dnaB mutations of Escherichia coli with thymineless death is described. All the isogenic Thy- dnaB mutants of E. coli we have tested show a remarkable immunity towards cell death induced by thymine deprivation at the nonpermissive temperature. We have also constructed and tested an isogenic double dnaB dnaG mutant. It loses its viability in the absence of thymine at both permissive and nonpermissive temperatures. The role of the dnaB gene product is discussed.

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Genetic effects of deoxyribonucleotide pool imbalances

Kunz

1982

Environ. mutagen

124

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In vivo DNA precursor imbalances can have profound genetic consequences in prokaryotes and eukaryotes. In vitro studies have demonstrated that DNA replication fidelity is dependent on correct balances of deoxyribonucleoside triphosphates during DNA synthesis. These findings suggest that intracellular concentrations of DNA precursors may be regulated in order to minimize the frequency of genetic change. In addition, they indicate the existence of important nonDNA targets for the induction of mutation, recombination, chromosome aberrations, etc. In this article, the genetic effects of deoxyribonucleotide pool imbalances are reviewed.

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Size and transforming activity of deoxyribonucleic acid in Diplococcus pneumoniae during thymidine starvation

Cited by 9 publications

References 26 publications

Sources of thymidine and analogs fueling futile damage-repair cycles and ss-gap accumulation during thymine starvation in Escherichia coli

Sources of thymidine and analogs fueling futile damage-repair cycles and ss-gap accumulation during thymine starvation in Escherichia coli

Thymineless death in Escherichia coli dnaB mutants and in a dnaB dnaG double mutant

Genetic effects of deoxyribonucleotide pool imbalances

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