Mfd Is Required for Rapid Recovery of Transcription following UV-Induced DNA Damage but Not Oxidative DNA Damage in Escherichia coli

Schalow, Brandy J.; Courcelle, Charmain T.; Courcelle, Justin

doi:10.1128/jb.06725-11

Cited by 31 publications

(32 citation statements)

References 72 publications

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“…Indeed, by “pushing” backtracked RNAP forward to resume transcription after UV exposure, Mfd should reduce the frequency of DNA breaks, which are often repaired in an error-prone fashion. This model is consistent with the requirement of Mfd for rapid recovery of transcription after DNA damage [51], and with the lag in post UV-irradiated growth of mfd(-) cells in liquid cultures due to excessively backtracked RNAPs (Kamarthapu and Nudler, unpublished data).…”

Section: Mfd-independent Tcrsupporting

confidence: 83%

Rethinking transcription coupled DNA repair

Kamarthapu

Nudler

2015

Current Opinion in Microbiology

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Nucleotide excision repair (NER) is an evolutionarily conserved, multistep process that can detect a wide variety of DNA lesions. Transcription coupled repair (TCR) is a sub-pathway of NER that repairs the transcribed DNA strand faster than the rest of the genome. RNA polymerase (RNAP) stalled at DNA lesions mediates the recruitment of NER enzymes to the damage site. In this review we focus on a newly identified bacterial TCR pathway in which the NER enzyme UvrD, in conjunction with NusA, plays a major role in initiating the repair process. We discuss the tradeoff between the new and conventional models of TCR, how and when each pathway operates to repair DNA damage, and the necessity of pervasive transcription in maintaining genome integrity.

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Section: Mfd-independent Tcrsupporting

confidence: 83%

Rethinking transcription coupled DNA repair

Kamarthapu

Nudler

2015

Current Opinion in Microbiology

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“…By ‘pushing’ backtracked RNAPs forward, Mfd suppresses DSBs associated with such collisions 39 , and hence diminishes the high frequency of mutations associated with DSBs repair. This model is consistent with the reduced ‘mutation frequency decline’ phenotype of mfd cells as well as their high UV mutability, minimal UV sensitivity 40 , and compromised transcriptional recovery after UV exposure 41 .…”

Section: Mfd-independent Tcrsupporting

confidence: 79%

UvrD facilitates DNA repair by pulling RNA polymerase backwards

Epshtein

Kamarthapu

McGary

et al. 2014

Nature

210

304

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UvrD helicase is required for nucleotide excision repair, although its role in this process is not well defined. Here we show that Escherichia coli UvrD binds RNA polymerase during transcription elongation and, using its helicase/translocase activity, forces RNA polymerase to slide backward along DNA. By inducing backtracking, UvrD exposes DNA lesions shielded by blocked RNA polymerase, allowing nucleotide excision repair enzymes to gain access to sites of damage. Our results establish UvrD as a bona fide transcription elongation factor that contributes to genomic integrity by resolving conflicts between transcription and DNA repair complexes. We further show that the elongation factor NusA cooperates with UvrD in coupling transcription to DNA repair by promoting backtracking and recruiting nucleotide excision repair enzymes to exposed lesions. Because backtracking is a shared feature of all cellular RNA polymerases, we propose that this mechanism enables RNA polymerases to function as global DNA damage scanners in bacteria and eukaryotes.

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“…Our hypothesis is that RNAPII is not arrested by oxidized bases but rather by products of their recognition, including depurination and/or the resulting single-nucleotide gap resulting from the activities of specialized glycosylases and endonucleases that initiate BER; the blocked RNAPII recruits TCR factors thus feeding into the NER pathway (Guo et al 2013). In E. coli , lack of Mfd activity does not affect lesion removal, survival or recovery of RNA synthesis after treatment with H 2 O 2 (Schalow et al 2012) indicating that in this organism there is no TCR of oxidized bases, or that TCR is not important for coping with oxidative damage; a role for UvrD/NusA remains to be elucidated. Oxidized guanine bases in DNA can be subject to further oxidation, leading to the formation of hydantoin lesions, which are highly mutagenic (McKibbin et al 2013).…”

Section: Tcr Of Non-bulky or Non-distorting Lesionsmentioning

confidence: 99%

Transcription-coupled repair: an update

Spivak

2016

Arch Toxicol

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Nucleotide excision repair (NER) is a versatile pathway that removes helix-distorting DNA lesions from the genomes of organisms across the evolutionary scale, from bacteria to humans. The serial steps in NER involve recognition of lesions, adducts or structures that disrupt the DNA double helix, removal of a short oligonucleotide containing the offending lesion, synthesis of a repair patch copying the opposite undamaged strand, and ligation, to restore the DNA to its original form. Transcription-coupled repair (TCR) is a subpathway of NER dedicated to the repair of lesions that, by virtue of their location on the transcribed strands of active genes, encumber elongation by RNA polymerases. In this review, I report on recent findings that contribute to the elucidation of TCR mechanisms in the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae and human cells. I review general models for the biochemical pathways and how and when cells might choose to utilize TCR or other pathways for repair or bypass of transcription-blocking DNA alterations.

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Mfd Is Required for Rapid Recovery of Transcription following UV-Induced DNA Damage but Not Oxidative DNA Damage in Escherichia coli

Cited by 31 publications

References 72 publications

Rethinking transcription coupled DNA repair

Rethinking transcription coupled DNA repair

UvrD facilitates DNA repair by pulling RNA polymerase backwards

Transcription-coupled repair: an update

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