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Replication Fork Stalling at Natural Impediments
Open accessAbstract
SUMMARY: Accurate and complete replication of the genome in every cell division is a prerequisite of genomic stability. Thus, both prokaryotic and eukaryotic replication forks are extremely precise and robust molecular machines that have evolved to be up to the task. However, it has recently become clear that the replication fork is more of a hurdler than a runner: it must overcome various obstacles present on its way. Such obstacles can be called natural impediments to DNA replication, as opposed to external and genetic factors. Natural impediments to DNA replication are particular DNA binding proteins, unusual secondary structures in DNA, and transcription complexes that occasionally (in eukaryotes) or constantly (in prokaryotes) operate on replicating templates. This review describes the mechanisms and consequences of replication stalling at various natural impediments, with an emphasis on the role of replication stalling in genomic instability.
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“collapse of the replication forks may result in DSBs [59].”
From Genomic instability and DNA damage responses in progeria arising from defective maturation of prelamin A (2009) · cites this paper as [59]
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“DSBs can be generated at stalled forks [59,62-64] that contain strand termini of double-stranded/single-stranded DNA (ds-ssDNA) junctions, mostly from Okazaki fragments.”
From Genomic instability and DNA damage responses in progeria arising from defective maturation of prelamin A (2009) · cites this paper as [59]
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Zhu, Y., Wang, Y., Tao, B., Han, J., Chen, H., Zhu, Q., Huang, L., He, Y., Hong, J., Li, Y., et al. (2021) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjab074 · Cited by 17
Henderson, M. L., & Kreuzer, K. N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128092 · Cited by 16
Bianco, P. R. (2020) · Genes · doi:10.3390/genes11050471 · Cited by 16
SLX4–XPF mediates DNA damage responses to replication stress induced by DNA–protein interactions
Ishimoto, R., Tsuzuki, Y., Matsumura, T., Kurashige, S., Enokitani, K., Narimatsu, K., Higa, M., Sugimoto, N., Yoshida, K., & Fujita, M. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202003148 · Cited by 17
DNA ligase 4 stabilizes the ribosomal DNA array upon fork collapse at the replication fork barrier
Fritsch, O., Burkhalter, M. D., Kais, S., Sogo, J. M., & Schär, P. (2010) · DNA repair · doi:10.1016/j.dnarep.2010.05.003 · Cited by 17
Recombination Phenotypes of Escherichia coli greA Mutants
Poteete, A. R. (2011) · BMC Molecular Biology · doi:10.1186/1471-2199-12-12 · Cited by 17
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Metadata
- Authors
- Mirkin, E. V., & Mirkin, S. M.
- Affiliations
- University of Illinois Chicago (US)
- ORCID
- Mirkin, Sergei M.
- Venue
- Microbiology and Molecular Biology Reviews
- Publisher
- American Society for Microbiology
- Published
- 2007-03
- Volume
- 71
- Issue
- 1
- Pages
- 13-35
- ISSN
- 1092-2172 (ISSN-L)
- 1098-5557
- PMC
- PMC1847372
- OpenAlex
- W2160336344
- Cited by
- 482
- References
- 316
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 14 · 2023: 23 · 2022: 15 · 2021: 28 · 2020: 42 · 2019: 30 · 2018: 32 · 2017: 27 · 2016: 38 · 2015: 22 · 2014: 34 · 2013: 29 · 2012: 32
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Microbiology and Molecular Biology Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM060987, GM60987)
- 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 › DNA and Nucleic Acid Chemistry
- Keywords
- replication fork stalling, DNA replication, genomic instability, DNA-binding proteins, DNA secondary structure, replication fork reversal
- MeSH terms
- Animals, DNA Replication, DNA-Binding Proteins, Humans, Models, Genetic, Transcription, Genetic, Replication Origin, Saccharomyces cerevisiae Proteins, Escherichia coli Proteins, Genomic Instability
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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