Largest Subunit Of RNA Polymerase Research Articles

Clitopilus lampangensis (Agaricales, Entolomataceae), a new species from northern Thailand.

A new species of agaricomycetes, Clitopilus lampangensis, is described based on collections from northern Thailand. This species was distinguished from previously described Clitopilus species by its pale yellow to grayish yellow pileus with the presence of wider caulocystidia. Molecular phylogenetic analyses, based on the data of the internal transcribed spacers (ITS) and the large subunit (LSU) of the nuclear ribosomal DNA, and the second largest subunit of RNA polymerase II (rbp2) genes, also support the finding that C. lampangensis is distinct from other species within the genus Clitopilus. A full description, color photographs, illustrations and a phylogenetic tree showing the position of C. lampangensis are provided.

Characterization of fungal species associated with cladode brown spot on Nopalea cochenillifera in Brazil

Cladode brown spot (CBS) is an important disease of Nopalea cochenillifera in the semiarid region of Northeastern Brazil. It has been reported in several countries, but its etiology is controversial, attributed to a complex of pathogens. Fifty fungal isolates were obtained and identified based on morphology and phylogeny, through analysis of the ribosomal DNA internal transcribed spacers (ITS), translation elongation factor 1-alpha (TEF1-alpha), β-tubulin (TUB-2), second largest subunit of RNA polymerase (RPB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the mating type locus MAT1–2 (ApMAT) partial gene sequences. Seven fungal general and twenty species were identified – Alternaria sp., A. longipes and A. tenuissima; Colletotrichum fructicola and C. siamense; Fusarium lunatum, F. incarnatum, and F. verticillioides; Lasiodiplodia euphorbicola, L. iraniensis, L. pseutheobromae, L. theobromae and Lasiodiplodia sp.; Neofusicoccum batangarum; Neopestalotiopsis australis, N. protearum and Neopestalotiopsis sp.; and Nigrospora sphaerica, N. hainanensis and Nigrospora sp. Four of these species had already been reported on Cactaceae of the genus Opuntia, but only N. batangarum, C. fructicola and C. siamense have been reported to date on the genus Nopalea. All isolates were pathogenic to detached cladodes of N. cochenillifera ‘Miuda’. Differences in aggressiveness were observed among the species, with L. iraniensis and F. lunatum characterized as the most aggressive species, whilst F. verticillioides as the least aggressive. This study provide important information on the fungi associated with cladode brown spot and improve the strategies for the management of disease on N. cochenillifera.

An overview of Antrodiella and related genera of Polyporales from the Neotropics

ABSTRACTThe genus Antrodiella includes resupinate and pileate species of polypores with a dimitic hyphal system, small, globose to cylindrical basidiospores, absence of cystidia, tetrapolar mating system, and haplo-dikaryotic nuclear behavior. Recent studies, however, indicate that Antrodiella is highly polyphyletic, so many of its species have been transferred to other genera. This study reviews the systematic status and diversity of Antrodiella from the Neotropics based, in part, on studies of type specimens. Collections from Brazil were used for molecular analysis of nuc rDNA internal transcribed spacer region ITS1‐5.8S‐ITS2 (ITS), nuc 28S rDNA (28S), and portions of genes encoding translation elongation factor 1-α (tef1) and the second largest subunit of RNA polymerase II (rpb2). Eight genera are confirmed to include Neotropical species treated as Antrodiella in a broad sense: Aegis, Antrodiella s. str., Flaviporus, Metuloidea, Mycorrhaphium, Rickiopora, Trametopsis, and Trullella. Molecular data reveal the occurrence of two new species, described as Antrodiella trivialis, the only Neotropical species of Antrodiella s. str. known so far, and Mycorrhaphium hispidum. In addition, Antrodiella luteocontexta was found to nest in the genus Aegis, close to the Grifolaceae and Polyporaceae; therefore, the new combination Aegis luteocontexta is proposed. Comments on the eight Antrodiella-related genera as well as species with uncertain taxonomic position are provided, together with a key to their identification.

A Role for Pre-mRNA-PROCESSING PROTEIN 40C in the Control of Growth, Development, and Stress Tolerance in Arabidopsis thaliana.

Because of their sessile nature, plants have adopted varied strategies for growing and reproducing in an ever-changing environment. Control of mRNA levels and pre-mRNA alternative splicing are key regulatory layers that contribute to adjust and synchronize plant growth and development with environmental changes. Transcription and alternative splicing are thought to be tightly linked and coordinated, at least in part, through a network of transcriptional and splicing regulatory factors that interact with the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II. One of the proteins that has been shown to play such a role in yeast and mammals is pre-mRNA-PROCESSING PROTEIN 40 (PRP40, also known as CA150, or TCERG1). In plants, members of the PRP40 family have been identified and shown to interact with the CTD of RNA Pol II, but their biological functions remain unknown. Here, we studied the role of AtPRP40C, in Arabidopsis thaliana growth, development and stress tolerance, as well as its impact on the global regulation of gene expression programs. We found that the prp40c knockout mutants display a late-flowering phenotype under long day conditions, associated with minor alterations in red light signaling. An RNA-seq based transcriptome analysis revealed differentially expressed genes related to biotic stress responses and also differentially expressed as well as differentially spliced genes associated with abiotic stress responses. Indeed, the characterization of stress responses in prp40c mutants revealed an increased sensitivity to salt stress and an enhanced tolerance to Pseudomonas syringae pv. maculicola (Psm) infections. This constitutes the most thorough analysis of the transcriptome of a prp40 mutant in any organism, as well as the first characterization of the molecular and physiological roles of a member of the PRP40 protein family in plants. Our results suggest that PRP40C is an important factor linking the regulation of gene expression programs to the modulation of plant growth, development, and stress responses.

Chromosome instability caused by mutations in the genes involved in transcription and splicing

ABSTRACTMutations in molecules involved in transcription and splicing can cause chromosome instability such as sister chromatid exchanges. We isolated and characterized responsible genes from mammalian temperature-sensitive mutant cells showing chromosome instability. A mutation in the largest subunit of RNA polymerase II affected DNA synthesis in S phase-arrested cells, resulting in abnormal induction of sister chromatid exchanges. The yeast mutant harboring a homologous mutation showed very similar phenotype to that of the mammalian mutant. A mutation in Smu1, which is involved in splicing, also affected DNA synthesis in S and G2 phase-arrested cells, resulting in abnormal induction of sister chromatid exchanges and chromosomal aberrations. These cells showed a connection between defects of RNA metabolism and induction of chromosome instability. Genome instability appeared to be caused by links between RNA metabolism and replication resulting in genomic recombination. RNA metabolism can be regarded as one possible driver of genome modification triggering genome evolution

Species borderlines in Fusarium exemplified by F. circinatum/F. subglutinans

Fusarium species are known as cross-kingdom pathogens, causing infections in both plants and animals. This ecological variation challenges the species concept of closely similar lineages in the genus. The present paper describes various types of genetic interaction between strains of two neighboring model species with different predilection, F. circinatum and F. subglutinans. Parameters include sequencing of the translation elongation factor 1α (TEF1) and the second largest subunit of RNA polymerase (RPB2), sexual crossing, and vegetative compatibility groups (VCGs). Successful interspecific crosses resulted in either recombination or in homothallic fruiting, the latter being limited to F. subglutinans MAT1 parents. Crossings were skewed, as Fusarium circinatum recombined more often than F. subglutinans. We hypothesize that genetic exchange in Fusarium species is finely regulated with an arsenal of options, which are applied when partners are phylogenetically closely related, leading to fluent species borderlines.

Expression of Meloidogyne incognita PolA1 hairpin RNA reduced nematode multiplication in transgenic tomato

Controlling root-knot nematodes (Meloidogyne spp.) using RNA interference (RNAi)-based molecular strategy is currently gaining consideration as a safer alternative to the use of chemical nematicides. However, identifying target genes whose knockdown in the parasites can effectively protect host plants is critical to success of this strategy. In this study, we transformed tomato plants to express hairpin RNA of Meloidogyne incognita-specific sequence (MiPA) of PolA1, an essential single-copy nuclear gene encoding the largest subunit of RNA polymerase I enzyme. We then evaluated nematode resistance in T1 transgenic lines for efficacy of host plant-mediated silencing of PolA1 gene in invading nematodes. We observed a significant reduction in nematode egg masses per plant root, eggs per egg mass and overall parasite multiplication in the transgenic plants compared to the wild type. Transgenic plants also had a reduced number of nematode galls per plant root than wild type but not significant. Although agronomic traits evaluated at the early growth stage were comparable in transgenics and wild types of tomato plants, production of MiPA-specific siRNAs in transgenic plants as well as the significant reduction of nematode PolA1 gene expression in feeding nematodes isolated from roots of transgenic plants provided evidence of host-induced gene silencing. Put together, our results are an indication that silencing of PolA1 gene is useful for reducing propagation of root-knot nematodes in tomato hosts. Its application to other crops may be possible and useful in improving agricultural productivity.

Abstract 373: Dysregulated RPB1 is a key driver of overgrowth and drug resistance in acute myeloid leukemia

Abstract Acute myeloid leukemia (AML) is a group of highly aggressive malignancies with a 5-year overall survival (OS) of <40%. Cell overgrowth with apoptosis resistance is a hallmark of AML, but little is known about how it occurs. In this study, we show that dysregulated the largest subunit of RNA polymerase II (RPB1) encoded by POLR2A gene is critically involved in this hallmark in AML. qRT-PCR and RNA-seq results showed that POLR2A mRNA were significantly overexpressed in 76.87% (113/147) compared with normal hematopoietic cells(1.5526 versus 0.8447, P<0.001). Western blotting analysis revealed that RPB1 protein is also aberrantly activated in 68.14%(67/113) of AML patients but rare or even absent in normal hematopoietic cells, (0.7889 versus 0.0509, P<0.01). TCGA data analysis indicated that aberrant activation of POLR2A mRNA occurred predominantly in AML, CHOL and THYM, but not in most other types of cancers. Importantly, we observed that RPB1 expression levels were closely associated with tumor burden and poor prognosis. Notably, we found that POLR2A inhibition induced potent apoptosis and growth inhibition of refractory AML cells. Global transcriptomic analysis reveals that POLR2A knockout selectively depleted an array of AML-related oncogenic and anti-apoptosis genes such as c-MYC, RUNX2, MEIS1, FLT3, CDC25A and BCL-2. Conversely, enforced overexpression of RPB1 exhibits robust enrichment of oncogenes and anti-apoptosis genes, leading to cell overgrowth and drug resistance. Of particular interesting, targeting RPB1 by both genetic and pharmacological molecules could lead complete regression of refractory human AML in mouse models. In conclusion, our findings for the first time reveal that dysregulated RPB1 is a central oncogenic hub that drives overgrowth and drug resistance by coordinately hijacking an array of oncogenic genes and anti-apoptosis factors. Importantly, RPB1 is not absolutely required for the survival of normal hematopoietic cells, which is contrary to the commonly accepted belief that RPB1, the heart of the cellular transcription machinery, is required for all protein-coding genes. These data suggest that targeting RPB1 might be a potential therapeutics for treating refractory/relapse AML. Note: This abstract was not presented at the meeting. Citation Format: Qingfeng Yu, Shu Zheng, Ying Xu, Rongzhen Xu. Dysregulated RPB1 is a key driver of overgrowth and drug resistance in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 373.

First Report of Fusarium oxysporum Causing Damping-off on Paprika in Korea

In February 2019, a damping-off disease occurred at the seedling stage of paprika in a commercial nursery located in Cheorwon, Korea. A species of Fusarium was isolated from the diseased plant and it was identified as Fusarium oxysporum based on morphological characteristics and nucleotide sequence data of translation elongation factor 1-α and the largest subunit of RNA polymerase. The isolate obtained was revealed to be pathogenic to the host plant through pathogenicity tests, and the reisolation of the pathogen confirmed Koch’s postulates. This is the first report of damping-off caused by Fusarium oxysporum on paprika in Korea.

Characterization of Fusarium and Neocosmospora Species Associated With Crown Rot and Stem Canker of Pistachio Rootstocks in California.

California produces 99.1% of pistachios grown in the United States, and diseases affecting pistachio rootstocks represent a constant challenge to the industry. Field surveys of fungi associated with pistachio rootstocks with symptoms of crown rot and stem canker in three central California counties followed by phylogenetic analyses of translation elongation factor 1-α and second largest subunit of RNA polymerase II gene fragments identified three Fusarium species (Fusarium equiseti, Fusarium oxysporum, and Fusarium proliferatum) and two Neocosmospora species (Neocosmospora falciformis and Neocosmospora solani). F. oxysporum and N. falciformis were the fungal species most frequently recovered from symptomatic pistachio trees. Inoculations of detached twigs of cultivar Kerman pistachio Pioneer Gold I and clonal University of California, Berkeley I (UCBI) rootstocks showed that all five species could colonize pistachio wood and cause vascular discolorations. Pathogenicity tests in potted pistachio trees completed Koch's postulates and confirmed that F. oxysporum, F. proliferatum, N. falciformis, and N. solani were capable of producing rot and discoloration in stems of clonal UCBI rootstocks, the most widely planted pistachio rootstock in California. To our knowledge, this study is the first to present insights into the biodiversity and biology of Fusarium and Neocosmospora species associated with pistachio trees in California.

BRAF inhibition sensitizes melanoma cells to \u03b1-amanitin via decreased RNA polymerase II assembly

Despite the great success of small molecule inhibitors in the treatment of patients with BRAFV600E mutated melanoma, the response to these drugs remains transient and patients eventually relapse within a few months, highlighting the need to develop novel combination therapies based on the understanding of the molecular changes induced by BRAFV600E inhibitors. The acute inhibition of oncogenic signaling can rewire entire cellular signaling pathways and thereby create novel cancer cell vulnerabilities. Here, we demonstrate that inhibition of BRAFV600E oncogenic signaling in melanoma cell lines leads to destabilization of the large subunit of RNA polymerase II POLR2A (polymerase RNA II DNA-directed polypeptide A), thereby preventing its binding to the unconventional prefoldin RPB5 interactor (URI1) chaperone complex and the successful assembly of RNA polymerase II holoenzymes. Furthermore, in melanoma cell lines treated with mitogen-activated protein kinase (MAPK) inhibitors, α-amanitin, a specific and irreversible inhibitor of RNA polymerase II, induced massive apoptosis. Pre-treatment of melanoma cell lines with MAPK inhibitors significantly reduced IC50 values to α-amanitin, creating a state of collateral vulnerability similar to POLR2A hemizygous deletions. Thus, the development of melanoma specific α-amanitin antibody-drug conjugates could represent an interesting therapeutic approach for combination therapies with BRAFV600E inhibitors.

Extension of the minimal functional unit of the RNA polymerase II CTD from yeast to mammalian cells

The carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) consists of 26 and 52 heptad-repeats in yeast and mammals, respectively. Studies in yeast showed that the strong periodicity of the YSPTSPS heptads is dispensable for cell growth and that di-heptads interspersed by spacers can act as minimal functional units (MFUs) to fulfil all essential CTD functions. Here, we show that the MFU of mammalian cells is significantly larger than in yeast and consists of penta-heptads. We further show that the distance between two MFUs is critical for the functions of mammalian CTD. Our study suggests that the general structure of the CTD remained largely unchanged in yeast and mammals; however, besides the number of heptad-repeats, also the length of the MFU significantly increased in mammals.

Multiple roles of CTDK-I throughout the cell.

The heterotrimeric carboxy-terminal domain kinase I (CTDK-I) in yeast is a cyclin-dependent kinase complex that is evolutionally conserved throughout eukaryotes and phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (RNApII) on the second-position serine (Ser2) residue of YSPTSPS heptapeptide repeats. CTDK-I plays indispensable roles in transcription elongation and transcription-coupled processing, such as the 3'-end processing of nascent mRNA transcripts. However, recent studies have revealed additional roles of CTDK-I beyond its primary effect on transcription by RNApII. Here, we describe recent advances in the regulation of genomic stability and rDNA integrity by CTDK-I and highlight the previously underappreciated cellular roles of CTDK-I in rRNA synthesis by RNA polymerase I and translational initiation and elongation. These multiple roles of CTDK-I throughout the cell expand our understanding of how this complex functions to coordinate diverse cellular processes through gene expression and how the human orthologue exerts its roles in diseased states such as tumorigenesis.

Species Diversity, Phylogeny, Divergence Time, and Biogeography of the Genus Sanghuangporus (Basidiomycota).

“Sanghuang” is a popular fungus used as a Chinese traditional medicine. In fact, it represents a group of fungi belonging to the genus Sanghuangporus, but little is known about its origin and biogeography. The aim of this study was to characterize the molecular relationships, origin and biogeographical distribution of Sanghuangporus. The multi-locus phylogenetic analyses were used to infer the phylogenetic relationships. In addition, based on Bayesian evolutionary analysis using sequences from the internal transcribed spacer (ITS), nuclear large subunit rDNA (nLSU), translation elongation factor 1-α (EF1-α), and the largest and second largest subunits of RNA polymerase II (RPB1 and RPB2), we used a fungus fossil-based approach to gain insight into the divergence time of species in Sanghuangporus. The molecular phylogeny strongly supports the monophyly of Sanghuangporus (MP = 100%, ML = 100%, and BPP = 1.00), and 13 species are recognized in this genus. The Bayesian uncorrelated lognormal relaxed molecular clock using BEAST and reconstructed ancestral areas indicate that the maximum crown age of Sanghuangporus is approximately 30.85 million years. East Asia is the likely ancestral area (38%). Dispersal and differentiation to other continents then occurred during the late Middle Miocene and Pliocene. The ancestor of Sanghuangporus probably originated in palaeotropical Northeast Asia and covered Northeast Asia and East Africa during the Oligocene-Miocene, hosted by plants that expanded via the “Gomphotherium Landbridge.” Six kinds of dispersal routes are proposed, including intercontinental dispersal events of three clades between Northeast Asia and East Africa, between East Asia and North America, and between Northeast Asia and Europe.

Two new taxa of the Auriscalpium vulgare species complex with substrate preferences

Basidiomes of the cone-inhabiting Auriscalpium species, usually regarded as A. vulgare Gray, are widely distributed across the Northern Hemisphere and easily recognized because of their unique macro-morphology. However, phylogenetic diversity patterns among different geographic populations and different substrates are completely unknown. In this study, samples of A. vulgare s.l. in different areas of China were studied phylogenetically, morphologically, and ecologically. For comparison, European collections of A. vulgare were included. Our phylogenetic analyses, inferred from partial nucleotide sequences including the internal transcribed spacers (ITS) 1 and 2 with the 5.8S nrDNA, the large subunit of nuclear ribosomal RNA (nrLSU), and the region between the conserved domain 6 and 7 of the gene for the second largest subunit of RNA polymerase II (RPB2), indicated that three phylogenetic species can be recognized, which correspond well with morphological and ecological evidence. Therefore, three species, having distinct substrate preferences, are documented here, namely the well-known A. vulgare, and the newly described species A. orientale and A. microsporum. Auriscalpium vulgare is widely distributed throughout the northern temperate Eurasia and North America, while the new species have been known mainly from subtropical East Asia and northeastern India to date.

Functional interaction of human Ssu72 with RNA polymerase II complexes

Phosphorylation of the C-terminal domain (CTD) of the large subunit of human RNA polymerase II (Pol II) is regulated during the transcription cycle by the combined action of specific kinases and phosphatases. Pol II enters into the preinitiation complex (PIC) unphosphorylated, but is quickly phosphorylated by Cdk7 during initiation. How phosphatases alter the pattern and extent of CTD phosphorylation at this early stage of transcription is not clear. We previously demonstrated the functional association of an early-acting, magnesium-independent phosphatase with early elongation complexes. Here we show that Ssu72 is responsible for that activity. We found that the phosphatase enters the transcription cycle during the formation of PICs and that Ssu72 is physically associated with very early elongation complexes. The association of Ssu72 with elongation complexes was stable to extensive washing with up to 200 mM KCl. Interestingly, Ssu72 ceased to function on complexes that contained RNA longer than 28 nt. However, when PICs were washed before initiation, the strict cutoff at 28 nt was lost. This suggests that factor(s) are important for the specific regulation of Ssu72 function during the transition between initiation and pausing. Overall, our results demonstrate when Ssu72 can act on early transcription complexes and suggest that Ssu72 may also function in the PIC prior to initiation.

Two new Neofomitella species (Polyporaceae, Basidiomycota) based on morphological and molecular evidence

Two new Neofomitella species, N. australiensis and N. guangxiensis, are described based on morphological and molecular characters. Neofomitella australiensis is characterized by white pore surface when fresh, dextrinoid skeletal and binding hyphae, and orange-red context near pileal surface when fresh. Neofomitella guangxiensis is characterized by round to angular pores (5–6 per mm), weakly dextrinoid skeletal and binding hyphae and large basidiospores (5.5–7.5 × 1.8–2.2 μm). Phylogenetic analyses were carried out based on sequences from the internal transcribed spacer (ITS), the large subunit nuclear ribosomal RNA gene (nLSU), the small subunit nuclear ribosomal RNA gene (nSSU), the small subunit mitochondrial rRNA gene (mtSSU), the translation elongation factor 1-α gene (EF1-α), the largest subunit of RNA polymerase II (RPB1) and the second largest subunit of RNA polymerase II (RPB2), and the result confirmed the affinities of the two new species within Neofomitella. An identification key to species of Neofomitella is provided.

Taxonomic revision of the genus Lactarius (Russulales, Basidiomycota) in Korea

The genus Lactarius Pers. (Russulales) is a cosmopolitan group of Basidiomycota that forms ectomycorrhizal relationships primarily with both deciduous and coniferous trees. Although the genus has been well-studied in Europe and North America, only fragmentary researches have been carried out on Asian species. In particular, the distribution of Lactarius species in South Korea is poorly understood due to insufficient morphological descriptions and a lack of DNA sequence data. In addition, the misuse of European and North American names has added to confusion regarding the taxonomy of Asian Lactarius species. In this study, the diversity of Lactarius in South Korea was evaluated by employing both morphological and phylogenetic approaches. A multi-locus phylogenetic analysis of 729 Lactarius specimens collected between 1960 and 2017 was performed using the internal transcribed spacer (ITS) region, partial nuclear ribosomal large subunit (nrLSU), partial second largest subunit of RNA polymerase II (rpb2), and minichromosome maintenance complex component 7 (mcm7). 49 Lactarius species were identified in three Lactarius subgenera: L. subg. Russularia (17 spp.), L. subg. Lactarius (22 spp.), and L. subg. Plinthogalus (10 spp.). Among them, 28 Lactarius species were identified as new to science, while just 17 were previously described Lactarius species. Four of the taxa remain un-named due to paucity of materials. A key to Korean Lactarius species, molecular phylogenies, a summary of diversity, and detailed description are provided.

Abstract P1-06-03: A selective Cdk12/13 non-covalent inhibitor with potent anti-breast cancer activity

Abstract Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) are Ser/Thr protein kinase members of the CDK family. CDKs are regulated by cyclins and members of the family are key regulators of the cell cycle. Other members of this family—CDK7, CDK8, CDK9, CDK12 and CDK13—have been described as transcription-regulating kinases. CDK12 and CDK13 phosphorylate the C-terminal domain (CTD) of rpb1 the largest subunit of RNA polymerase II and interact with RNA processing factors, playing pivotal roles controlling transcription initiation and elongation, as well as posttranscriptional RNA processing. Specifically, CDK12 acts as the limiting factor for the transcription of a small subset of genes that are involved in the DNA damage response pathway and CDK13 affects expression of genes involved in growth signaling pathways. Importantly, like their cell cycle family members CDK12 and CDK13 have also been shown to be promising therapeutic targets for several cancer types. We have generated a novel, selective, and orally bioavailable, small molecule inhibitor of CDK12 and CDK13. Our lead molecule downregulates key DNA damage repair proteins including ATM, ATR, Brca1 and Rad51 leading to induction of apoptotic cell death in all triple negative breast cancer (TNBC) cell lines tested. We have confirmed the selectivity of our compound by kinase profiling and by comparing the gene expression profile by RNA-seq of cells treated with compound or infected with CRISPR sgRNA targeting Cdk12 and/or Cdk13. Importantly, our compound acts in synergy with the chemotherapeutic agents Cisplatin, Irinotecan and Olaparib. Finally, in preclinical efficacy studies, our lead compound blocked tumor progression in two different PDX models of TNBC and demonstrated tumor regression and enhanced efficacy over single treatment when dosed in combination with selected chemotherapeutic agents. Citation Format: Quereda V, Bayle S, Francesca V, Andrii M, William R, Derek D. A selective Cdk12/13 non-covalent inhibitor with potent anti-breast cancer activity [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-06-03.

Victoriomyces antarcticus gen. nov., sp. nov., a distinct evolutionary lineage of the Cephalothecaceae (Ascomycota) based on sequence-based phylogeny and morphology.

In this study, we propose a new genus, Victoriomyces, with a new species, Victoriomyces antarcticus, isolated from soil samples collected in Victoria Land, Antarctica. To determine its taxonomic status and evolutionary relationships, phylogenetic analysis was performed on DNA sequences from the nuclear 18S rRNA, 28S rRNA and the second largest subunit of RNA polymerase II (RPB2) genes. Victoriomyces antarcticus constitutes one well-supported distinct lineage within the Cephalothecaceae (family incertae sedis in Sordariomycetes), in which the only recognised asexual morphs belong to the genus Phialemonium and to Acremonium thermophilum. Victoriomyces antarcticus can be clearly distinguished from these taxa by means of DNA sequence analysis and its morphological traits that consist in having a Metarhizium-like asexual morph, dark red-coloured disk-like structures, immature bodies and the production of an intense red pigment in the growth media. Finally, we inferred the divergence time of V. antarcticus and the Cephalothecaceae using Bayesian analysis and secondary calibration. The holotype of V. antarcticus is FBL 165. The ex-type strain has been deposited as MUT 3686T and CCF 6158T. An additional strain of the species is FBL 577. The MycoBank number is MB 823713 for the genus and MB 823714 for the species.