Crucial role and mechanism of transcription-coupled DNA repair in bacteria

Bharati, Binod K.; Gowder, Manjunath; Zheng, Fangfang; Alzoubi, Khaled M.; Svetlov, Vladimir; Kamarthapu, Venu; Weaver, Jacob W; Epshtein, Vitaly; Vasilyev, Nikita; Shen, Liqiang; Zhang, Yu; Nudler, Evgeny

doi:10.1038/s41586-022-04530-6

Cited by 41 publications

(39 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1B). This is consistent with recent biochemical findings regarding NER and transcription and brings into question whether GG-NER is a mechanism that exists 10 .…”

Section: Discussionsupporting

confidence: 92%

“…1B). This is consistent with recent biochemical findings regarding NER and transcription and brings into question whether GG-NER is a mechanism that exists 10 . Interestingly, our data show that it is the cooperative nature of at least two DNA polymerases that causes NER-dependent mutations: the replicative polymerase commonly associated with NER, PolA, and one of two redundant Y-family polymerases, PolY1 and PolY2 (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…The damage containing oligo is removed by the UvrD helicase and the pathway is fished by gap filling DNA synthesis 5 . A recent alternative model for damage recognition during TC-NER suggests that UvrD instead of Mfd recruits the NER factors and proposes that, in bacteria, all NER is transcription coupled, although these conclusions remain somewhat controversial [7][8][9][10] .…”

Section: Main Textmentioning

confidence: 99%

See 2 more Smart Citations

Oxidative stress drives mutagenesis through transcription coupled repair in bacteria

Carvajal-Garcia

Samadpour

Viera

et al. 2022

Preprint

View full text Add to dashboard Cite

Nucleotide excision repair (NER) is a highly conserved mechanism that removes lesions from DNA. This process has been studied for decades, however, almost all of the work on NER was performed in the presence of exogenous DNA damage. Under these conditions, NER is anti-mutagenic in bacteria. Here, we describe our findings on the role of NER in mutagenesis under endogenous conditions. Counter to dogma, we find that NER is actually pro-mutagenic. Our data suggest a hand-off mechanism between two different types of DNA polymerases that explains the mutagenic nature of NER. Additionally, NER is thought to occur in two different ways; 1) in a transcription-coupled manner where it plays a role in removing lesions that block RNA polymerase, and 2) in a process known as global genome NER, which is independent of transcription. Counter to the classical view, our genetic analyses of the relationship between NER and the RNA polymerase interacting DNA translocase, and evolvability factor, Mfd, indicate that most likely all NER is associated with transcription. Lastly, we show that NER is pro-mutagenic because of endogenous oxidative damage. Altogether, our data strongly suggest that oxidative damage induces a mutagenic NER mechanism, which then accelerates evolution across divergent bacterial species.

show abstract

“…1B). This is consistent with recent biochemical findings regarding NER and transcription and brings into question whether GG-NER is a mechanism that exists 10 .…”

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Main Textmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress drives mutagenesis through transcription coupled repair in bacteria

Carvajal-Garcia

Samadpour

Viera

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition to the expected transcription coupled repair of lesions on the template strand, we also used multiallelic variation rates to demonstrate transcription associated repair of non-template strand lesions. In prokaryotes, this phenomenon can occur as a consequence of antisense transcription 46 , but mutation spectra reveal that is not the case in these mammalian tumours. We therefore propose that transcription associated repair represents enhanced genome-wide NER surveillance of more accessible, expressed genes.…”

Section: Discussionmentioning

confidence: 99%

Strand-resolved mutagenicity of DNA damage and repair

Anderson

Talmane

Luft

et al. 2022

Preprint

View full text Add to dashboard Cite

SummaryDNA base damage is a major source of oncogenic mutations1. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation2. Here, we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication3,4, we observe identical fidelity and damage tolerance for both strands. For small DNA adducts, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky adducts5. We find that DNA damage tolerance is also common during transcription, where RNA-polymerases frequently bypass lesions without triggering repair. At multiple genomic scales, we show the pattern of DNA damage induced mutations is largely shaped by the influence of DNA accessibility on repair efficiency, rather than gradients of DNA damage. Finally, we reveal specific genomic conditions that can corrupt the fidelity of nucleotide excision repair and actively drive oncogenic mutagenesis. These results provide insight into how strand-asymmetric mechanisms underlie the formation, tolerance, and repair of DNA damage, thereby shaping cancer genome evolution.

show abstract

“…UvrD interacts directly with RNAP but the functional importance of this interaction has been unclear until recently (47–50). UvrD has been suggested to promote backtracking of stalled RNAP as a first step in transcription-coupled repair (50, 51); however, other studies argue against UvrD playing any role in coupling nucleotide excision repair to stalled transcription complexes (48, 49, 52–56). Here, we combined state-of-the-art live cell imaging using single-molecule microscopy with advanced biochemical activity experiments in vitro to elucidate how UvrD resolves replicative blocks.…”

Section: Introductionmentioning

confidence: 99%

Tetrameric UvrD helicase is located at theE. colireplisome due to frequent replication blocks

Wollman

Syeda

Leech

et al. 2021

Preprint

View full text Add to dashboard Cite

DNA replication in all organisms must overcome nucleoprotein blocks to complete genome duplication. Accessory replicative helicases in Escherichia coli, Rep and UvrD, help replication machinery overcome blocks by removing incoming nucleoprotein complexes or aiding the re-initiation of replication. Mechanistic details of Rep function have emerged from recent live cell studies, however, the activities of UvrD in vivo remain unclear. Here, by integrating biochemical analysis and super-resolved single-molecule fluorescence microscopy, we discovered that UvrD self-associates into a tetramer and, unlike Rep, is not recruited to a specific replisome protein despite being found at approximately 80% of replication forks. By deleting rep and DNA repair factors mutS and uvrA, perturbing transcription by mutating RNA polymerase, and antibiotic inhibition; we show that the presence of UvrD at the fork is dependent on its activity. This is likely mediated by the very high frequency of replication blocks due to DNA bound proteins, including RNA polymerase, and DNA damage. UvrD is recruited to sites of nucleoprotein blocks via distinctly different mechanisms to Rep and therefore plays a more important and complementary role than previously realised in ensuring successful DNA replication.

show abstract

Crucial role and mechanism of transcription-coupled DNA repair in bacteria

Cited by 41 publications

References 106 publications

Oxidative stress drives mutagenesis through transcription coupled repair in bacteria

Oxidative stress drives mutagenesis through transcription coupled repair in bacteria

Strand-resolved mutagenicity of DNA damage and repair

Tetrameric UvrD helicase is located at theE. colireplisome due to frequent replication blocks

Contact Info

Product

Resources

About