The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Increased global transcription activity as a mechanism of replication stress in cancer
Open accessAbstract
Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS V12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS V12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
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Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
Comprehensive molecular characterization of gastric adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13480 · Cited by 6,498
Comprehensive molecular profiling of lung adenocarcinoma
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Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
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The Somatic Genomic Landscape of Glioblastoma
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Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place
Kotsantis, P., Petermann, E., & Boulton, S. J. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1461 · Cited by 416
Self-citationZirkel, A., Nikolic, M., Sofiadis, K., Mallm, J.-P., Brackley, C. A., Gothe, H., Drechsel, O., Becker, C., Altmüller, J., Josipovic, N., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.030 · Cited by 226
DNA damage and transcription stress
Milano, L., Gautam, A., & Caldecott, K. W. (2024) · Molecular Cell · doi:10.1016/j.molcel.2023.11.014 · Cited by 88
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Giordano, A. M. S., Luciani, M., Gatto, F., Abou Alezz, M., Beghè, C., Della Volpe, L., Migliara, A., Valsoni, S., Genua, M., Dzieciatkowska, M., et al. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20211121 · Cited by 76
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Metadata
- Authors
- Kotsantis, P., Silva, L. M., Irmscher, S., Jones, R. M., Folkes, L., Gromak, N., & Petermann, E.
- Venue
- Nature Communications
- Published
- 2016-10-11
- Volume
- 7
- Issue
- 1
- Pages
- 13087-13087
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2531499154
- Cited by
- 336
- References
- 64
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- gold
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