ArticleGenes & development2011
The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 303 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
303 citing papers in PubMed, 1 synthesis or guideline pooled it, 519 citations in OpenAlex.
- PARP inhibitors as a new therapeutic option in metastatic prostate cancer: a systematic review.Prostate cancer and prostatic diseases · 2020Pooled it
- Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.Nature communications · 2022Trial
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- Inhibition of CDK12/CDK13-CYCLIN K rewires P-TEFb signaling to reverse HIV-1 latency and modulate cellular gene expression.EMBO molecular medicine · 2026Article
- CDK12/13 inhibition overcomes platinum resistance by impairing RNA metabolism.Signal transduction and targeted therapy · 2026Article
- Communication is key: combinatorial phosphorylation and functional cross-talk in the RNA polymerase II CTD code.Biochemical Society transactions · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Pan-cancer multi-omics characterization of CDK12 and virtual screening of Vietnamese natural products for novel inhibitors.Molecular diversity · 2026Article
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- CDK12 mediates the inhibition effect of mechanical unloading on osteoblast proliferation by regulating RNAPII transcription activation.Bone & joint research · 2026Article
- Breast cancer genomic subtype-specific copy number alterations in metastases.Scientific reports · 2026Article
- Loss of the tumor suppressor PTEN activates cell-intrinsic interferon signaling to drive immune resistance.Genes & development · 2026Article
- RNA-binding proteins TDP-43 and FUS promote R-loop resolution and regulate transcription termination.The Journal of biological chemistry · 2026Article
- Research Progress of PROTACs in Breast Cancer: Subtype-Oriented Target Landscape, Clinical Stratification Evidence, and Engineering Strategies for Translation.Biomedicines · 2026Review
- Absence of synergistic effects by CDK12/13 inhibition in combination with cisplatin or olaparib in ovarian cancer cells.Scientific reports · 2026Article
- Inactivation of CDK12 Enhances Mitochondrial Efficiency to Suppress DNA Damage.Journal of cellular and molecular medicine · 2026Article
- The Emerging Role of Transcription-Associated Cyclin-Dependent Kinases in Gastrointestinal Tumors.Cancers · 2026Review
- Targeting CDK12 disrupts estrogen-receptor chromatin recruitment and ER-MED1 transcription in advanced ER+ breast cancer.Journal of the National Cancer Institute · 2026Article
243 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Various cyclin-dependent kinase (Cdk) complexes have been implicated in the regulation of transcription. In this study, we identified a 70-kDa Cyclin K (CycK) that binds Cdk12 and Cdk13 to form two different complexes (CycK/Cdk12 or CycK/Cdk13) in human cells. The CycK/Cdk12 complex regulates phosphorylation of Ser2 in the C-terminal domain of RNA polymerase II and expression of a small subset of human genes, as revealed in expression microarrays. Depletion of CycK/Cdk12 results in decreased expression of predominantly long genes with high numbers of exons. The most prominent group of down-regulated genes are the DNA damage response genes, including the critical regulators of genomic stability: BRCA1 (breast and ovarian cancer type 1 susceptibility protein 1), ATR (ataxia telangiectasia and Rad3-related), FANCI, and FANCD2. We show that CycK/Cdk12, rather than CycK/Cdk13, is necessary for their expression. Nuclear run-on assays and chromatin immunoprecipitations with RNA polymerase II on the BRCA1 and FANCI genes suggest a transcriptional defect in the absence of CycK/Cdk12. Consistent with these findings, cells without CycK/Cdk12 induce spontaneous DNA damage and are sensitive to a variety of DNA damage agents. We conclude that through regulation of expression of DNA damage response genes, CycK/Cdk12 protects cells from genomic instability. The essential role of CycK for organisms in vivo is further supported by the result that genetic inactivation of CycK in mice causes early embryonic lethality.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.