The Roles of Bacterial DNA Double-Strand Break Repair Proteins in Chromosomal DNA Replication

Sinha, Anurag Kumar; Possoz, Christophe; Leach, David R. F.

doi:10.1093/femsre/fuaa009

Cited by 35 publications

(44 citation statements)

References 142 publications

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“…Since the discovery of the RecD role in cold-adaptation, a quest to understand DNA-repair processes at low temperature has revealed the importance of DNA-repair genes such as recC, recB, recF, recO, recR, recJ, and ruvAB in cold adaptation of P. syringae (Pavankumar et al, 2010;Sinha et al, 2013;Sinha et al, 2020). As described in this section, the RecBCD-and…”

Section: Role Of the Recfor Pathway In Dna Repairmentioning

confidence: 96%

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Molecular insights into the ecology of a psychrotolerant Pseudomonas syringae

Pavankumar

Mittal

Hallsworth

2020

Environmental Microbiology

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Low temperatures constrain cellular life due to reductions in nutrient uptake, enzyme kinetics, membrane permeability, and function of other biomacromolecules. This has implications for the biophysical limits of life on Earth, and the plausibility of life in extraterrestrial locations. Although most pseudomonads are mesophilic in nature, isolates such as the Antarctic Pseudomonas syringae Lz4W exhibit considerable psychrotolerance, with an ability to grow even between 4 and 0 C. In this review, we explore the molecular traits and characteristic phenotypes of P. syringae Lz4W that enable life at low temperatures. We describe adaptations that enhance membrane fluidity; examine genes involved in cellular function and survival in the cold; assess capability for energy generation at low temperature; and detail the mechanics of DNA repair and RNA processing at low temperature, and speculate that P. syringae Lz4W can also synthesize glycerol to maintain flexibility of macromolecular systems. In the range 4 to 0ºC, there are considerable changes in the properties and behaviour of water. Specifically, density can have adverse impacts on plasma-membrane functions, cytoplasmic viscosity, protein behaviour, and other essential properties of cellular system. We identified a combination of adaptations that may be peculiar to cold-tolerant P. syringae, including increase of unsaturated fatty acids in the plasma membrane; a RNA polymerase able to function at 0 C; RecBCD-and RuvAB-dependent reestablish ment of replication fork; and efficiencies of degradosome machinery and RNA processing by RNaseR at low temperature. Several unresolved questions are discussed in the context of astrobiology, and further work needed on the psychrotolerance of P. syringae.

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Section: Role Of the Recfor Pathway In Dna Repairmentioning

confidence: 96%

“…In E. coli, RecBCD and RecFOR pathways are the two major DNA repair-pathways that repair DSBs and single-strand DNA gaps via homologous recombination (Spies and Kowalczykowski, 2005;Sinha et al, 2020). (Ivancic-Bace et al, 2005;Sinha et al, 2020).…”

Section: Role Of the Recfor Pathway In Dna Repairmentioning

confidence: 99%

Molecular insights into the ecology of a psychrotolerant Pseudomonas syringae

Pavankumar

Mittal

Hallsworth

2020

Environmental Microbiology

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“…Faithful damage repair orchestrated by DNA repair proteins is essential to maintain genomic integrity, chromosomal replication and cell viability. Accordingly, mutants lacking repair proteins are sensitive to DNA damaging agents and are less viable ( Van Houten, 1990 ; Kuzminov, 1999 ; Sinha et al, 2020 ). Since (p)ppGpp binding to RNAP in E. coli destabilizes the open promoter complexes, it is expected to modulate replication-transcription collision and to play a role in maintaining genomic integrity.…”

Section: Role Of the Stringent Response In Dna Damage And Repairmentioning

confidence: 99%

“…The observation that loss of both RelA and SpoT (ppGpp 0 strain), i.e., inability to synthesize (p)ppGpp, enhanced UV sensitivity of an E. coli ruvAB mutant, suggested a possible role of (p)ppGpp in facilitating DNA repair ( McGlynn and Lloyd, 2000 ). RuvAB along with RuvC play a role in branch migration and resolution of Holliday junctions, formed during RecBCD-RecA-mediated DNA double-strand break (DSB) repair and RecFOR-RecA-mediated gap repair ( Kuzminov, 1999 ; Sinha et al, 2020 ). Interestingly, a slight increase in the basal level of (p)ppGpp by using the spoT1 allele, having reduced (p)ppGpp hydrolytic activity, improved UV survival of the ruvAB mutant ( McGlynn and Lloyd, 2000 ).…”

Section: Role Of the Stringent Response In Dna Damage And Repairmentioning

confidence: 99%

Bacterial Chromosome Replication and DNA Repair During the Stringent Response

2020

Self Cite

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The stringent response regulates bacterial growth rate and is important for cell survival under changing environmental conditions. The effect of the stringent response is pleiotropic, affecting almost all biological processes in the cell including transcriptional downregulation of genes involved in stable RNA synthesis, DNA replication, and metabolic pathways, as well as the upregulation of stress-related genes. In this Review, we discuss how the stringent response affects chromosome replication and DNA repair activities in bacteria. Importantly, we address how accumulation of (p)ppGpp during the stringent response shuts down chromosome replication using highly different strategies in the evolutionary distant Gram-negative Escherichia coli and Grampositive Bacillus subtilis. Interestingly, (p)ppGpp-mediated replication inhibition occurs downstream of the origin in B. subtilis, whereas replication inhibition in E. coli takes place at the initiation level, suggesting that stringent cell cycle arrest acts at different phases of the replication cycle between E. coli and B. subtilis. Furthermore, we address the role of (p)ppGpp in facilitating DNA repair activities and cell survival during exposure to UV and other DNA damaging agents. In particular, (p)ppGpp seems to stimulate the efficiency of nucleotide excision repair (NER)-dependent repair of DNA lesions. Finally, we discuss whether (p)ppGpp-mediated cell survival during DNA damage is related to the ability of (p)ppGpp accumulation to inhibit chromosome replication.

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“…It has also been suggested that extended RNAP backtracking could be associated with R-loop formation from the 3'-end of the nascent RNA (40,46). R-loops are physiological initiators of ColE1 plasmid replication (47), but in addition their excessive occurrence (as in rnhA mutants) can lead to pathological initiation of chromosomal DNA replication in both bacteria (reviewed in [48][49][50] and eukaryotes (51). Such aberrant replication in bacteria is referred to as constitutive stable DNA replication (cSDR) since, unlike ordinary chromosomal replication which is initiated at oriC with the aid of the unstable protein DnaA, it continues long after inhibition of protein synthesis in the cells.…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase I Essentiality, DnaA-independent Chromosomal Replication, and Transcription-Replication Conflict inEscherichia coli

Leela

Raghunathan

Gowrishankar

2021

Preprint

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Topoisomerase I (Topo I) of <Escherichia coli, encoded by topA, acts to relax negative supercoils in DNA. Topo I deficiency results in hypernegative supercoiling, formation of transcription-associated RNA-DNA hybrids (R-loops), and DnaA- and oriC-independent constitutive stable DNA replication (cSDR), but some uncertainty persists as to whether topA is essential for viability in E. coli and related enterobacteria. Here we show that several topA alleles, including ΔtopA>, confer lethality in derivatives of wild-type E. coli strain MG1655. Viability in absence of Topo I was restored with two perturbations, neither of which reversed the hypernegative supercoiling phenotype: (i) in a reduced-genome strain MDS42, or (ii) by an RNA polymerase (RNAP) mutation rpoB*35 that has been reported to alleviate the deleterious consequences of RNAP backtracking and transcription-replication conflicts. Four phenotypes related to cSDR were identified for topA mutants: (i) One of the topA alleles rescued ΔdnaA lethality; (ii) in dnaA+ derivatives, Topo I deficiency generated a characteristic copy number peak in the terminus region of the chromosome; (iii) topA was synthetically lethal with rnhA (encoding RNase HI, whose deficiency also confers cSDR); and (iv) topA rnhA synthetic lethality was itself rescued by ΔdnaA. We propose that the terminal lethal consequence of hypernegative DNA supercoiling in E. colitopA mutants is RNAP backtracking during transcription elongation and associated R-loop formation, which in turn lead to transcription-replication conflicts and to cSDR.

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The Roles of Bacterial DNA Double-Strand Break Repair Proteins in Chromosomal DNA Replication

Cited by 35 publications

References 142 publications

Molecular insights into the ecology of a psychrotolerant Pseudomonas syringae

Molecular insights into the ecology of a psychrotolerant Pseudomonas syringae

Bacterial Chromosome Replication and DNA Repair During the Stringent Response

Topoisomerase I Essentiality, DnaA-independent Chromosomal Replication, and Transcription-Replication Conflict inEscherichia coli

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