Dicer promotes transcription termination at sites of replication stress to maintain genome stability.

Nuclear RNAi is an important regulator of transcription and epigenetic modification, but the underlying mechanisms remain elusive. Using a genome-wide approach in the fission yeast S. pombe, we have found that Dcr1, but not other components of the canonical RNAi pathway, promotes the release of Pol II from the 3? end of highly transcribed genes, and, surprisingly, from antisense transcription of rRNA and tRNA genes, which are normally transcribed by Pol I and Pol III.

Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in human breast cancer by affecting DNA damage response.

Vaccinia-related kinase 1 (VRK1) belongs to a group of sixteen kinases associated to a poorer prognosis in human breast carcinomas, particularly in estrogen receptor positive cases based on gene expression arrays. In this work we have studied the potential molecular mechanism by which the VRK1 protein can contribute to a poorer prognosis in this disease. For this aim it was first analyzed by immunohistochemistry the VRK1 protein level in normal breast and in one hundred and thirty six cases of human breast cancer.

VRK1 interacts with p53 forming a basal complex that is activated by UV-induced DNA damage.

DNA damage immediate cellular response requires the activation of p53 by kinases. We found that p53 forms a basal stable complex with VRK1, a Ser-Thr kinase that responds to UV-induced DNA damage by specifically phosphorylating p53. This interaction takes place through the p53 DNA binding domain, and frequent DNA-contact mutants of p53, such as R273H, R248H or R280K, do not disrupt the complex.

Roles of VRK1 as a new player in the control of biological processes required for cell division.

Cell division, in addition to an accurate transmission of genetic information to daughter cells, also requires the temporal and spatial coordination of several biological processes without which cell division would not be feasible. These processes include the temporal coordination of DNA replication and chromosome segregation, regulation of nuclear envelope disassembly and assembly, chromatin condensation and Golgi fragmentation for its redistribution into daughter cells, among others. However, little is known regarding regulatory proteins and signalling pathways that might participate in the coordination of all these different biological functions.

Downregulation of VRK1 by p53 in response to DNA damage is mediated by the autophagic pathway.

Human VRK1 induces a stabilization and accumulation of p53 by specific phosphorylation in Thr18. This p53 accumulation is reversed by its downregulation mediated by Hdm2, requiring a dephosphorylated p53 and therefore also needs the removal of VRK1 as stabilizer. This process requires export of VRK1 to the cytosol and is inhibited by leptomycin B.

The C/H3 domain of p300 is required to protect VRK1 and VRK2 from their downregulation induced by p53.

Background: The vaccinia-related kinase 1 (VRK1) protein, an activator of p53, can be proteolytically downregulated by an indirect mechanism, which requires p53-dependent transcription.

Principal Findings: In this work we have biochemically characterized the contribution of several p53 transcriptional cofactors with acetyl transferase activity to the induction of VRK1 downregulation that was used as a functional assay. Downregulation of VRK1 induced by p53 is prevented in a dose dependent manner by either p300 or CBP, but not by PCAF, used as transcriptional co-activators, suggesting that p53 has a different specificity depending on the relative level of these transcriptional cofactors.

Human VRK1 is an early response gene and its loss causes a block in cell cycle progression.

Background: In mammalian cells regulatory proteins controlling the cell cycle are necessary due to the requirements of living in a heterogeneous environment of cell-interactions and growth factors. VRK1 is a novel serine-threonine kinase that phosphorylates several transcription factors and is associated with proliferation phenotypes.

Methodology/principal Findings: In this report VRK1 has been identified as regulated in the cell cycle.

Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas.

Human VRK1 (vaccinia-related kinase 1) is a novel serine-threonine kinase that regulates several transcription factors, including p53, ATF2 and c-Jun; and its loss results in defects of cell proliferation. VRK1 stabilizes p53 and the accumulated p53 downregulates VRK1 forming an autoregulatory loop. Wild-type p53, but not mutant p53, was able to downregulate VRK1 in the A549 lung carcinoma cell line.

Identification of a dominant epitope in human vaccinia-related kinase 1 (VRK1) and detection of different intracellular subpopulations.

The human VRK1 is a new ser-thr kinase expressed in many cell types. VRK1 is a regulator of p53 and other transcription factors related with cellular responses to stress. The human VRK1 protein has a dominant epitope located in its C-terminal region, between residues 333 and 396, which is detected by different antibodies.

p53 downregulates its activating vaccinia-related kinase 1, forming a new autoregulatory loop.

The stable accumulation of p53 is detrimental to the cell because it blocks cell growth and division. Therefore, increases in p53 levels are tightly regulated, mainly by its transcriptional target, mdm2, that downregulates p53. Elucidation of new signaling pathways requires the characterization of the members and the nature of their connection.

VRK1 signaling pathway in the context of the proliferation phenotype in head and neck squamous cell carcinoma.

The vaccinia-related kinase (VRK) proteins are a new family with three members in the human kinome. The VRK1 protein phosphorylates several transcription factors and has been postulated to be involved in regulation of cell proliferation. In normal squamous epithelium, VRK1 is expressed in the proliferation area.