Abstract
Spatial patterns of transcriptional activity in the living genome of Escherichia coli represent one of the more peculiar aspects of the E. coli chromosome biology. Spatial transcriptional correlations can be observed throughout the chromosome, and their formation depends on the state of replication in the cell. The condition of thymine starvation leading to thymineless death (TLD) is at the “cross-roads” of replication and transcription. According to a current view, e.g., (Cagliero et al., 2014), one of the cellular objectives is to segregate the processes of transcription and replication in time and space. An ultimate segregation would take place when one process is inhibited and another is not, as it happens during thymine starvation, which results in numerous molecular and physiological abnormalities associated with TLD. One of such abnormalities is the loss of spatial correlations in the vicinity of the origin of replication. We review the transcriptional consequences of replication inhibition by thymine starvation in a context of the state of DNA template in the starved cells and opine about a possible significance of normal physiological coupling between the processes of replication and transcription.
Highlights
Replication and transcription are intertwined in a number of ways, as molecular reactions and biological processes
A study by Jeong et al (2006) demonstrated, using mutants with conditionally defective initiation of chromosomal DNA replication, that ongoing replication is required for observing spatial patterns across scales
These results are consistent with a model according to which DNA template collapses at the replication origin and its neighborhood either as a result of degradation of nascent leading and lagging DNA strands in both chromatids or from a random, relatively short patch degradation of parental and nascent DNA, in both chromatids (Sangurdekar et al, 2010). Both interpretations imply that DNA in the region may be degenerated to a point where it can no longer be used as a template in the reaction of transcription, explaining why any transcriptional patterns in that region might be degraded. This view is complicated by an observation that thymine deprived cells continue transcribing genes in the region of the lesion well into starvation and even during the killing phase of thymineless death (TLD) (Sangurdekar et al, 2010): half-life of a representative E. coli mRNA is about 60 times shorter than the timeline of a typical thymine starvation experiment (Bernstein et al, 2002) and there is no indication that mRNA stability is affected under conditions of thymine starvation, and the average abundance of transcripts from the region in question changes less than 50% in the course of the starvation (Sangurdekar et al, 2010)
Summary
Replication and transcription are intertwined in a number of ways, as molecular reactions and biological processes. Perturbed states of the bacterial chromosome (Kaguni, 2006) controls, as an activator and repressor, transcription of the ribonucleotide reductase operon (Olliver et al, 2010) Sixth, activity of both processes can be modulated by (p)ppGpp (Chiaramello and Zyskind, 1990; Levine et al, 1991; Denapoli et al, 2013) and by changes in DNA supercoiling (Kowalski and Eddy, 1989; Crooke et al, 1991; von Freiesleben and Rasmussen, 1992; Peter et al, 2004; Rovinskiy et al, 2012), two molecular sensors that can relay information about critical fluctuations in the cell’s environment to the parts of the replication and transcription machineries (Dorman, 2006; Jin et al, 2012; Sobetzko et al, 2012). Nowhere such consequences are more pronounced than during thymine starvation
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