How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between DNA Repair and Transcription

Sivaramakrishnan, Priya; Gordon, Alasdair J.E.; Halliday, Jennifer A.; Herman, Christophe

doi:10.1002/bies.201800045

Cited by 4 publications

(3 citation statements)

References 70 publications

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“…Thus, nascent RNA structures can block backtracking (156) and antisense DNAs or RNAs that create nascent structures can be used to assess the contribution of backtracking to pausing (4). Extensive backtracking leads to EC arrest, from which it is important to rescue or remove RNAP (e.g., by GreB-stimulated transcript cleavage or by Mfd) to avoid collisions with replication that cause double-stranded breaks in DNA (132). Thus, backtrack pausing plays central roles both in maintaining information in DNA and in accurately copying information to RNA.…”

Section: Backtrack Pause Signalsmentioning

confidence: 99%

Transcriptional Pausing as a Mediator of Bacterial Gene Regulation

Landick

2021

Annu. Rev. Microbiol.

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Cellular life depends on transcription of DNA by RNA polymerase to express genetic information. RNA polymerase has evolved not just to read information from DNA and write it to RNA but also to sense and process information from the cellular and extracellular environments. Much of this information processing occurs during transcript elongation, when transcriptional pausing enables regulatory decisions. Transcriptional pauses halt RNA polymerase in response to DNA and RNA sequences and structures at locations and times that help coordinate interactions with small molecules and transcription factors important for regulation. Four classes of transcriptional pause signals are now evident after decades of study: elemental pauses, backtrack pauses, hairpin-stabilized pauses, and regulator-stabilized pauses. In this review, I describe current understanding of the molecular mechanisms of these four classes of pause signals, remaining questions about how RNA polymerase responds to pause signals, and the many exciting directions now open to understand pausing and the regulation of transcript elongation on a genome-wide scale. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Backtrack Pause Signalsmentioning

confidence: 99%

Transcriptional Pausing as a Mediator of Bacterial Gene Regulation

Landick

2021

Annu. Rev. Microbiol.

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“…Proteins involved in DNA replication, repair, and transcription share the same DNA template and coordination between these processes is indispensable in preventing conflicts, which could result in genomic instability. Studies in E. coli have pinpointed a role of RNAP secondary channel interactors in modulating transcription conflicts with replication as well as DNA repair machineries 22,43,44 . Here, we investigate how the modulation of RNAP processivity influences DSB repair in the presence of a DNA end-binding protein, MuGam.…”

Section: Discussionmentioning

confidence: 99%

Modulation of RNA polymerase processivity affects double-strand break repair in the presence of a DNA end-binding protein

Sivaramakrishnan

Bradley

Artsimovitch

et al. 2022

Preprint

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Homologous recombination (HR) is the predominant mechanism for double-strand DNA break repair in Escherichia coli, but recently non-homologous end joining (NHEJ) was described involving the Ku-like GAM protein of bacteriophage Mu (MuGam), sparking interest into its biology and utility as a model for a DNA-end binding protein. MuGam binds to DNA ends, but how it interferes with DNA repair enzymes or transcription in living cells remains elusive. In E. coli, RNA polymerase secondary channel interactors, such as DksA and GreA, have been shown to play a role in the coordination of transcription with DNA replication and break repair. Here we show that MuGam inhibits break repair by slowing down RecBCD resection and impeding HR in live bacteria. Loss of GreA restores DNA break repair in the presence of MuGam, in part by releasing MuGam from the DNA. Furthermore, using MuGam as a DNA break sensor, we found that DSBs are generated when translation is inhibited and more so in the presence of GreA supporting the model where uncoupling of transcription and translation increases transcription/replication collisions. Significantly, this work reveals that modulation of RNA polymerase processivity can impact DNA break repair in presence of a Ku-like protein.

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“…backtracked complexes can provoke conflicts of transcription with DNA replication resulting in DNA damage but at the same time can stimulate repair of double-strand breaks in DNA (7,17,48,49). Since the suppressor mutations increase cell survival under DNA damaging conditions, we tested whether they can affect nucleotide misincorporation, TEC backtracking, and RNA cleavage.…”

Section: Minor Effects Of Rnap Mutations On Rna Cleavage and Mismatch...mentioning

confidence: 99%

Suppressor mutations in Escherichia coli RNA polymerase alter transcription initiation but do not affect translesion RNA synthesis in vitro

Miropolskaya

Petushkov

Esyunina

et al. 2022

Journal of Biological Chemistry

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How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between DNA Repair and Transcription

Cited by 4 publications

References 70 publications

Transcriptional Pausing as a Mediator of Bacterial Gene Regulation

Transcriptional Pausing as a Mediator of Bacterial Gene Regulation

Modulation of RNA polymerase processivity affects double-strand break repair in the presence of a DNA end-binding protein

Suppressor mutations in Escherichia coli RNA polymerase alter transcription initiation but do not affect translesion RNA synthesis in vitro

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