The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses
Open accessAbstract
Summary Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells. R-loops, but not normal transcription complexes, induce DNA breaks and orientation-specific DNA damage responses during conflicts with replication forks. Unexpectedly, the replisome acts as an orientation-dependent regulator of R-loop levels, reducing R-loops in the co-directional (CD) orientation but promoting their formation in the head-on (HO) orientation. Replication stress and deregulated origin firing increase the number of HO collisions leading to genome-destabilizing R-loops. Our findings connect DNA replication to R-loop homeostasis and suggest a mechanistic basis for genome instability resulting from deregulated DNA replication, observed in cancer and other disease states.
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Cites
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Self-citationOncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
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Cited by
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The DNA damage response to transcription stress
Lans, H., Hoeijmakers, J. H. J., Vermeulen, W., & Marteijn, J. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0169-4 · Cited by 321
Zatreanu, D., Han, Z., Mitter, R., Tumini, E., Williams, H., Gregersen, L., Dirac-Svejstrup, A. B., Roma, S., Stewart, A., Aguilera, A., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.037 · Cited by 124
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Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response
Mandal, J., Mandal, P., Wang, T.-L., & Shih, I.-M. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00856-5 · Cited by 84
Metadata
- Authors
- Hamperl, S., Bocek, M. J., Saldivar, J. C., Swigut, T., & Cimprich, K. A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 170
- Issue
- 4
- Pages
- 774-786.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2743954317
- Cited by
- 646
- References
- 10
- FWCI
- 18.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hamperl, S., Bocek, M. J., Saldivar, J. C., Swigut, T., & Cimprich, K. A. (2017). Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses. Cell. https://doi.org/10.1016/j.cell.2017.07.043
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