Direct restart of a replication fork stalled by a head-on RNA polymerase
Open accessAbstract
When Polymerases Collide: Genomes must be replicated by DNA polymerase and copied by RNA polymerase. The two processes occur concurrently in bacteria and, although the majority of bacterial genes are co-oriented with replication, head-on collisions still occur and can result in double-strand breaks in the genome. Pomerantz and O'Donnell (p. 590 ) show, in vitro, that both Escherichia coli DNA and RNA polymerases grind to a halt when they collide bumper to bumper but that the replication fork remains intact, with the RNA polymerase being shunted off the DNA and out of the way. Mfd, a transcription-repair coupling factor, promotes DNA replication restart probably by rewinding separated DNA stands ahead of the halted transcription complex, promoting its displacement from the DNA.
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Looping out of control: R-loops in transcription-replication conflict
Kumar, C., & Remus, D. (2023) · Chromosoma · doi:10.1007/s00412-023-00804-8 · Cited by 34 · see citing works
“Biochemical studies involving reconstituted replisomes suggest that RNAPs sterically block replisome progression (Liu and Alberts 1995; Pomerantz and O’Donnell 2010; Bruning and Marians 2020) (Fig.”
The bacterial DNA repair protein Mfd confers resistance to the host nitrogen immune response
Guillemet, E., Leréec, A., Tran, S., Royer, C., Barbosa, I., Sansonetti, P., Lereclus, D., & Ramarao, N. (2016) · Scientific Reports · doi:10.1038/srep29349 · Cited by 34
Replisome bypass of transcription complexes and R-loops
Brüning, J.-G., & Marians, K. J. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa741 · Cited by 39 · see citing works
“Our data on collisions between replisomes and transcription complexes is in agreement with what has been published previously for collisions between the replisome and a single transcription complex (11,66).”
Visualizing Protein Movement on DNA at the Single-molecule Level using DNA Curtains
Silverstein, T., Gibb, B., & Greene, E. (2014) · DNA Repair · doi:10.1016/j.dnarep.2014.02.004 · Cited by 32
Baharoglu, Z., Babosan, A., & Mazel, D. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1259 · Cited by 38 · see citing works
“Direct restart of the replication fork can take place after displacement of the stalled RNAP, as the replisome is stable enough to wait for the stalled RNAP to be dislodged (58).”
Poveda, A., Clech, M. L., & Pasero, P. (2010) · Transcription · doi:10.4161/trns.1.2.12665 · Cited by 40 · see citing works
“coli, the replisome moves 15 to 30 times faster than transcription complexes and the replication machinery can also rear-end RNA polymerases.(8,9) In general, the replisome is given priority and RNAP are displaced.”
Esyunina, D., Turtola, M., Pupov, D., Bass, I., Klimašauskas, S., Belogurov, G. A., & Kulbachinskiy, A. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1521 · Cited by 30 · see citing works
Stability of blocked replication forks in vivo
Mettrick, K. A., & Grainge, I. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1079 · Cited by 31 · see citing works
“These studies indicate DnaC is not necessary for an active replisome, and evidence suggests DnaC dissociates from the DNA once DnaB interacts with DnaG (10); indeed active priming complexes do not contain DnaC (25) and replication has been found to be able to proceed in vitro in the absence of DnaC (7,26,27).”
Transcriptional De-Repression and Mfd Are Mutagenic in Stressed Bacillus subtilis Cells
Martin, H. A., Pedraza‐Reyes, M., Yasbin, R. E., & Robleto, E. A. (2011) · Microbial Physiology · doi:10.1159/000332751 · Cited by 29 · see citing works
“Observations from those studies suggest that encounters between replication and transcription may cause genome instability, particularly in the absence of transcription elongation factors mediating the removal of paused RNAP complexes [Pomerantz and O’Donnell, 2010; Tehranchi et al., 2010].”
Transcription-replication coordination revealed in single live cells
Tsirkas, I., Dovrat, D., Thangaraj, M., Brouwer, I., Cohen, A., Paleiov, Z., Meijler, M. M., Lenstra, T. L., & Aharoni, A. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac069 · Cited by 34 · see citing works
“The absence of dramatic fork stalling indicates that after collision, the replisome stays intact and quickly resumes DNA replication, consistent with the in vitro study described above (48).”
A Proposal: Source of single strand DNA that elicits the SOS response
Indiani, C. (2012) · Frontiers in bioscience · doi:10.2741/4102 · Cited by 25 · see citing works
“An in vitro study utilized RNA polymerase, among the tightest of DNA binding proteins, to test the stability of the replication fork upon encounter with a transcribing RNA polymerase (21).”
Self-citationReplication Through Repetitive DNA Elements and Their Role in Human Diseases
Madireddy, A., & Gerhardt, J. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-6955-0_23 · Cited by 32 · see citing works
Revet, I. M., Feeney, L., Tang, A. A., Huang, E. J., & Cleaver, J. E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202621109 · Cited by 25 · see citing works
“We reported this work in preliminary fashion, hinting that we had discovered specific down-regulation of collagen 15a1 and latrophilin (9).”
Genomic landscape of single-stranded DNA gapped intermediates in Escherichia coli
Pham, P., Shao, Y., Cox, M. M., & Goodman, M. F. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1269 · Cited by 22 · see citing works
“The range of lengths for hot regions is sufficient to accommodate the many cellular processes involved in ssDNA generation, going from a low of ∼1–12 kb ssDNA gaps for base and nucleotide excision repair (45,46), to a high of ∼50–2 kb ssDNA gaps associated with homologous recombination, post-replication mismatch repai…”
A Primase-Induced Conformational Switch Controls the Stability of the Bacterial Replisome
Monachino, E., Jergic, S., Lewis, J. S., Xu, Z.-Q., Lo, A. T., O'Shea, V. L., Berger, J., Dixon, N., & van Oijen, A. V. (2018) · bioRxiv · doi:10.1101/469312 · Cited by 23
“…observed by a constant template utilization as a function of [DnaGC]), and (vi) DnaB is reported to be stable on ssDNA for very long periods (~60 min; Pomerantz and O’Donnell, 2010), we conclude that the progressively higher efficiencies in DNA synthesis are due to a DnaGC-induced strengthening…”
Cancer Therapy and Replication Stress
Kotsantis, P., Jones, R. M., Higgs, M. R., & Petermann, E. (2015) · Advances in clinical chemistry · doi:10.1016/bs.acc.2014.12.003 · Cited by 24 · see citing works
Sequential eviction of crowded nucleoprotein complexes by the exonuclease RecBCD molecular motor
Terakawa, T., Redding, S., Silverstein, T. D., & Greene, E. C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701368114 · Cited by 22 · see citing works
Darrigo, C., Guillemet, E., Dervyn, R., & Ramarao, N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163321 · Cited by 22
Lee, S., Su, G., Lasserre, E., Aghazadeh, M. A., & Murai, N. (2012) · Plant Science · doi:10.1016/j.plantsci.2012.01.012 · Cited by 22
Helicases that underpin replication of protein-bound DNA in Escherichia coli
McGlynn, P. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390606 · Cited by 20 · see citing works
Brugger, C., Zhang, C., Suhanovsky, M. M., Kim, D. D., Sinclair, A. N., Lyumkis, D., & Deaconescu, A. M. (2020) · Nature Communications · doi:10.1038/s41467-020-17457-1 · Cited by 23 · see citing works
A Proteomic Study of Memory After Imprinting in the Domestic Chick
Meparishvili, M., Nozadze, M., Margvelani, G., McCabe, B. J., & Solomonia, R. O. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00319 · Cited by 23 · see citing works
Genomic patterns of transcription–replication interactions in mouse primary B cells
Germain, C. S., Zhao, H., Sinha, V., Sanz, L. A., Chedin, F. L., & Barlow, J. H. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac035 · Cited by 29 · see citing works
“Studies in bacterial systems show that both co-directional and head-on transcription can induce replication fork stalling and collapse, the latter causing more profound consequences (17-24).”
Martin, H. A., Porter, K. E., Vallin, C., Ermi, T., Contreras, N., Pedraza‐Reyes, M., & Robleto, E. A. (2019) · BMC Microbiology · doi:10.1186/s12866-019-1394-x · Cited by 21 · see citing works
Back to the Origin: Reconsidering Replication, Transcription, Epigenetics, and Cell Cycle Control
Evertts, A. G., & Coller, H. A. (2012) · Genes & Cancer · doi:10.1177/1947601912474891 · Cited by 20 · see citing works
“When DNA polymerases encounter barriers, one possibility is that the blockage is removed and the polymerase can continue.(21) Other possible outcomes can result in errors in the passage of genetic information, for instance, single-stranded DNA and DNA breaks can be formed, which can lead to singlestranded 3′ tails fro…”
Dealing with Transcriptional Outbursts during S Phase to Protect Genomic Integrity
Duch, A., de Nadal, E., & Posas, F. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.08.019 · Cited by 16 · see citing works
Transcription-Replication Collisions—A Series of Unfortunate Events
Germain, C. S., Zhao, H., & Barlow, J. H. (2021) · Biomolecules · doi:10.3390/biom11081249 · Cited by 22 · see citing works
Yakhnin, A., Bubunenko, M., Mandell, Z. F., Lubkowska, L., Husher, S., Babitzke, P., & Kashlev, M. (2023) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2221114120 · Cited by 16
Interplay of DNA repair with transcription: from structures to mechanisms
Deaconescu, A. M., Artsimovitch, I., & Grigorieff, N. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.09.002 · Cited by 14 · see citing works
The replication-transcription conflict
Soultanas, P. (2011) · Transcription · doi:10.4161/trns.2.3.15908 · Cited by 15 · see citing works
Bypass of complex co-directional replication-transcription collisions by replisome skipping
Brüning, J.-G., & Marians, K. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab760 · Cited by 14
“For example, the helicases Rep and UvrD and the translocase Mfd can promote replisome bypass at head-on replication-transcription collisions (22,31,53).”
Deaconescu, A. M. (2021) · Transcription · doi:10.1080/21541264.2021.1982628 · Cited by 16 · see citing works
“In vitro, Mfd mediates direct restart of a replisome colliding with RNAP head-on by dismantling the TEC [94], but upon co-directional collisions, replisomes can restart by reinitiating from an mRNA primer without the aid of Mfd [95].”
Molecular Highways—Navigating Collisions of DNA Motor Proteins
Le, T. T., & Wang, M. D. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.08.006 · Cited by 14 · see citing works
A link between transcription fidelity and pausing in vivo
Gamba, P., James, K., & Zenkin, N. (2017) · Transcription · doi:10.1080/21541264.2016.1274812 · Cited by 14 · see citing works
“Head-on collisions with transcribing RNAP are more severe and have been shown to arrest the replication forks both in vivo and in vitro.(27) Accordingly, highly-expressed, long, and essential genes are preferentially located on the leading strand in bacterial genomes,(15) and genetic instability following head-on coll…”
Undesigned selection for replication termination of bacterial chromosomes.
Kono, N., Arakawa, K., Sato, M., Yoshikawa, H., Tomita, M., & Itaya, M. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.06.005 · Cited by 14
Cooper, D. L., Harada, T., Tamazi, S., Ferrazzoli, A. E., & Lovett, S. T. (2021) · mBio · doi:10.1128/mbio.00184-21 · Cited by 16 · see citing works
Direct visualization of replication and R-loop collision using single-molecule imaging
Kim, S., Shin, W.-H., Kang, Y.-J., Kim, H., & Lee, J. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1101 · Cited by 12
“Consistent with our results, many previous studies about TRCs re-ported that HO collision is more deleterious than CD collision ( 66 ,67 ) .”
- Authors
- Pomerantz, R. T., & O’Donnell, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- O’Donnell, Mike
- Venue
- Science
- Published
- 2010-01-29
- Volume
- 327
- Issue
- 5965
- Pages
- 590-592
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2861996
- OpenAlex
- W2086307439
- Cited by
- 150
- References
- 27
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 15 · 2015: 9 · 2014: 7 · 2013: 17 · 2012: 14
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (R01GM038839)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- replication fork restart, replication fork stalling, replisome, transcription-coupled repair, Mfd, Escherichia coli, DNA replication, transcription-replication conflict
- MeSH terms
- Bacterial Proteins, DNA-Directed DNA Polymerase, DNA Repair, DNA Replication, DNA, Bacterial, Escherichia coli, DNA-Directed RNA Polymerases, Templates, Genetic, Transcription Factors, Transcription, Genetic, Escherichia coli Proteins
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