Oncogenic mutations impede nuclear RNA surveillance.

RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We found that disrupted nuclear RNA surveillance is oncogenic. Cyclin-dependent kinase 13 () is mutated in melanoma, and patient-mutated accelerates zebrafish melanoma.

CDK12 regulates DNA repair genes by suppressing intronic polyadenylation.

Mutations that attenuate homologous recombination (HR)-mediated repair promote tumorigenesis and sensitize cells to chemotherapeutics that cause replication fork collapse, a phenotype known as 'BRCAness'. BRCAness tumours arise from loss-of-function mutations in 22 genes. Of these genes, all but one (CDK12) function directly in the HR repair pathway.

Dynamic transcription factor activity and networks during ErbB2 breast oncogenesis and targeted therapy.

Tissue development and disease progression are multi-stage processes controlled by an evolving set of key regulatory factors, and identifying these factors necessitates a dynamic analysis spanning relevant time scales. Current omics approaches depend on incomplete biological databases to identify critical cellular processes. Herein, we present TRACER (TRanscriptional Activity CEll aRrays), which was employed to quantify the dynamic activity of numerous transcription factor (TFs) simultaneously in 3D and networks for TRACER (NTRACER), a computational algorithm that allows for cellular rewiring to establish dynamic regulatory networks based on activity of TF reporter constructs.