RNA Polymerase II subunits overexpressions induce genome instability and deregulate transcription
Sadurni, M. M.; Jones, M. L.; Pavlou, L.; Radi, M.; Kompocholi, S.; Passaretti, P.; Gambus, A.; Gregersen, L. H.; Saponaro, M.
Show abstract
Independently of the pathways or circuits deregulated in cancer cells, these present altered transcription patterns, often also direct consequence of deregulation of transcription factors. In this sense, also the RNA Polymerase complexes responsible for transcription can be affected in cancers. We find that upregulations of RNA Polymerase II subunits, especially the largest ones, correlates with poor cancer patients outcome across a range of tumor types, presenting increased genome instability. Overexpressing the subunits RPB1, RPB3 and RPB4 in cells we find that these induce DNA damage. However, the mechanisms behind this increased genome instability are specific for each subunit, linked to the unique transcription alterations generated by the subunit overexpression. Importantly, we find significant overlap between the genes with more DNA damage in our cell line models and those more affected in cancers with subunit upregulation, indicating that upregulations could be responsible for some of the phenotypes present in these patients.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The PIN1-p38-CtIP signaling axis protects stalled replication forks from deleterious degradation 96%
- SETDB1 Fuels the Lung Cancer Phenotype by Modulating Epigenome, 3D Genome Organization and Chromatin Mechanical Properties 96%
- Cytoplasmic Switch of ARS2 Isoforms Promotes Nonsense-Mediated mRNA Decay and Arsenic Sensitivity 96%
Similar papers in this journal
- PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity 97%
- Alkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression 97%
- 3D genome organization during TGFB-induced transcription requires nuclear microRNA and G-quadruplexes 96%
Similar papers in this journal
- Metabolism-dependent secondary effect of anti-MAPK cancer therapy on DNA repair 95%
- Gene essentiality in cancer is better predicted by mRNA abundance than by gene regulatory network-inferred activity 93%
- The DNA Damage Response (DDR) landscape of endometrial cancer defines discrete disease subtypes and reveals therapeutic opportunities. 93%
Similar papers in this journal
- Sequential deregulation of histone marks, chromatin accessibility and gene expression in response to PROTAC-induced degradation of ASH2L 97%
- Transcriptome-wide high-throughput mapping of protein-RNA occupancy profiles using POP-seq 96%
- Active regulatory elements recruit cohesin to establish cell-specific chromatin domains. 95%
"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.