The cohesin-like RecN protein stimulates RecA-mediated recombinational repair of DNA double-strand breaks

Uranga, Lee A.; Reyes, Emigdio D.; Patidar, Praveen; Redman, Lindsay N.; Lusetti, Shelley L.

doi:10.1038/ncomms15282

Cited by 42 publications

(41 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we reasoned that the increased early survival of mistranslating strains must be aided by faster or more efficient repair and recombination. To test this, we deleted RecN-a key member of the SOS-linked recombination mediated repair pathway [44]. The deletion decreased early survival upon Cip exposure ( Fig 3C) and led to a complete loss of Cip resistance ( Fig 3D), indicating that repair and recombination functions indeed underlie the increased Cip resistance observed in the mistranslating Mutant.…”

Section: Mistranslation Mediates Ciprofloxacin Resistance Via the Sosmentioning

confidence: 98%

Global mistranslation increases cell survival under stress in Escherichia coli

2020

View full text Add to dashboard Cite

Mistranslation is typically deleterious for cells, although specific mistranslated proteins can confer a short-term benefit in a particular environment. However, given its large overall cost, the prevalence of high global mistranslation rates remains puzzling. Altering basal mistranslation levels of Escherichia coli in several ways, we show that generalized mistranslation enhances early survival under DNA damage, by rapidly activating the SOS response. Mistranslating cells maintain larger populations after exposure to DNA damage, and thus have a higher probability of sampling critical beneficial mutations. Both basal and artificially increased mistranslation increase the number of cells that are phenotypically tolerant and genetically resistant under DNA damage; they also enhance survival at high temperature. In contrast, decreasing the normal basal mistranslation rate reduces cell survival. This wideranging stress resistance relies on Lon protease, which is revealed as a key effector that induces the SOS response in addition to alleviating proteotoxic stress. The new links between error-prone protein synthesis, DNA damage, and generalised stress resistance indicate surprising coordination between intracellular stress responses and suggest a novel hypothesis to explain high global mistranslation rates. Author summaryCells make mistakes all the time. Protein synthesis is exceptionally error-prone, which is puzzling because such mistakes are usually harmful. Prior work shows that specific erroneous proteins can be beneficial under specific stresses. However, this cannot explain a high background error rate, because most mistakes will not be useful. We offer a solution to this conundrum: cells that make more mistakes accumulate a key quality-control enzyme, tripping the switch for a broad stress response (the "SOS" response, that repairs damaged DNA). In turn, this increases cell survival. The unexpected link between protein synthesis and DNA damage suggests surprising cross talk across important quality-control processes, and motivates a new hypothesis to explain how and why cells tolerate so many mistakes.

show abstract

Section: Mistranslation Mediates Ciprofloxacin Resistance Via the Sosmentioning

confidence: 98%

Global mistranslation increases cell survival under stress in Escherichia coli

2020

View full text Add to dashboard Cite

show abstract

“…A). More recently, RecN has been shown to stimulate RecA’s ability to catalyze D‐loop formation in vitro (Uranga et al , ) (Fig. A).…”

Section: Resultsmentioning

confidence: 96%

“…(2) RecN is also thought to perform an endjoining function during double‐strand break repair (Meddows et al, ; Grove et al, ). (3) RecN may interact with RecA to facilitate homology search and strand invasion during homologous recombination of double‐strand breaks (Uranga et al, ). Note that in all sections, whether RecN is diagrammed as part of a dimer or polymer, it is pictured as either an open circle or a helical structure as suggested by Pellegrino et al ().…”

Section: Resultsmentioning

confidence: 99%

Protease‐deficient SOS constitutive cells have RecN‐dependent cell division phenotypes

Warr

Klimova

Nwaobasi

et al. 2018

Molecular Microbiology

View full text Add to dashboard Cite

In Escherichia coli, after DNA damage, the SOS response increases the transcription (and protein levels) of approximately 50 genes. As DNA repair ensues, the level of transcription returns to homeostatic levels. ClpXP and other proteases return the high levels of several SOS proteins to homeostasis. When all SOS genes are constitutively expressed and many SOS proteins are stabilized by the removal of ClpXP, microscopic analysis shows that cells filament, produce mini-cells and have branching protrusions along their length. The only SOS gene required (of 19 tested) for the cell length phenotype is recN. ClpXP or recN4174 (A552S, A553V), a mutant not recognized by ClpXP, produce filamentous cells with nucleoid partitioning defects. It is hypothesized that when produced at high levels during the SOS response, RecN interferes with nucleoid partitioning and Z-Ring function by holding together sections of the nucleoid, or sister nucleoids, providing another way to inhibit cell division. RecN is a member of the Structural Maintenance of Chromosome (SMC) class of proteins. It can hold pieces of DNA together and is important for doublestrand break repair (DSBR). RecN is degraded by ClpXP. Overexpression of recN + in the absence of

show abstract

Section: Resultsmentioning

confidence: 99%

Global mistranslation facilitates sampling of beneficial mutations under stress

Samhita

Agashe

2019

Preprint

View full text Add to dashboard Cite

11Mistranslation is typically deleterious, but can sometimes be beneficial. Although a specific 12 mistranslated protein can confer a short-term benefit in a particular environment, the prevalence of high 13 global mistranslation rates remains puzzling given the large overall cost. Here, we show that generalized 14 mistranslation enhances early E. coli survival under various forms of DNA damage, because it leads to 15 early activation of the DNA damage-induced SOS response. Mistranslating cells therefore maintain 16 larger populations, facilitating later sampling of critical beneficial mutations. Thus, under DNA 17 damage, both basal and induced mistranslation (through genetic or environmental means) increase the 18 number of genetically resistant and phenotypically persistent cells. Surprisingly, mistranslation also 19 increases survival at high temperature. This wide-ranging stress resistance relies on Lon protease, which 20 is revealed as a key effector that induces the SOS response in addition to alleviating proteotoxic stress. 21The new links between error-prone protein synthesis, DNA damage, and generalised stress resistance 22 indicate surprising coordination between intracellular stress responses, and suggest a novel hypothesis 23 to explain high global mistranslation rates. 24 25

show abstract

The cohesin-like RecN protein stimulates RecA-mediated recombinational repair of DNA double-strand breaks

Cited by 42 publications

References 60 publications

Global mistranslation increases cell survival under stress in Escherichia coli

Global mistranslation increases cell survival under stress in Escherichia coli

Protease‐deficient SOS constitutive cells have RecN‐dependent cell division phenotypes

Global mistranslation facilitates sampling of beneficial mutations under stress

Contact Info

Product

Resources

About