SAMHD1 promotes oncogene-induced replication stress
Zhang, S. M.; Calderon-Montano, J. M.; Rudd, S. G.
Show abstract
Oncogenes induce DNA replication stress in cancer cells. Although this was established more than a decade ago, we are still unravelling the molecular underpinnings of this phenomenon, which will be critical if we are to exploit this knowledge to improve cancer treatment. A key mediator of oncogene-induced replication stress is the availability of DNA precursors, which will limit ongoing DNA synthesis by cellular replicases. In this study, we identify a potential role for nucleotide catabolism in promoting replication stress induced by oncogenes. Specifically, we establish that the dNTPase SAMHD1 slows DNA replication fork speeds in human fibroblasts harbouring an oncogenic RAS allele, elevating levels of endogenous DNA damage, and ultimately limiting cell proliferation. We then show that oncogenic RAS-driven tumours express reduced SAMHD1 levels, suggesting they have overcome this tumour suppressor barrier, and that this correlates with worse overall survival for these patients. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/226282v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@bb425forg.highwire.dtl.DTLVardef@2a1b7org.highwire.dtl.DTLVardef@c70bf3org.highwire.dtl.DTLVardef@1e1b028_HPS_FORMAT_FIGEXP M_FIG C_FIG
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Oncogenic RAS sensitizes cells to drug-induced replication stress via transcriptional silencing of P53 96%
- The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival 94%
- Loss of EIF4G2 Mediates Aggressiveness in Distinct Human Endometrial Cancer Subpopulations with Poorer Survival Outcome in Patients 94%
Similar papers in this journal
- Pro-survival roles for p21(Cip1/Waf1) in Non-Small Cell Lung Cancer 96%
- Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer 93%
- Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting 93%
Similar papers in this journal
- DNA replication during acute MEK inhibition drives acquisition of resistance through amplification of the BRAF oncogene 95%
- Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells 94%
- High-grade Ovarian Cancer Associated H/ACA snoRNAs Promote Cancer Cell Proliferation and Survival 94%
Similar papers in this journal
Similar papers in this journal
- Heterogeneity of RNA editing in mesothelioma and how RNA editing enzyme ADAR2 affects mesothelioma cell growth, response to chemotherapy and tumor microenvironment 94%
- USP28 enables oncogenic transformation of respiratory cells and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K. 94%
- Targeting LDHC dysregulates the cell cycle and improves sensitivity to cisplatin and olaparib 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.