DNA polymerase ε associates with the elongating form of RNA polymerase II and nascent transcripts

Rytkönen, Anna K.; Hillukkala, Tomi; Vaara, Markku; Sokka, Miiko; Jokela, Maarit; Sormunen, Raija; Nasheuer, Heinz-Peter; Nethanel, Tamar; Kaufmann, Gabriel; Pospiech, Helmut; Syväoja, Juhani E.

doi:10.1111/j.1742-4658.2006.05544.x

Cited by 9 publications

(8 citation statements)

References 72 publications

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“…Double staining used 5-and 10-nm gold particles to label Bet v 1 and caveolin 2, respectively (see the Methods section in this article's Online Repository). 18 Specimens from 3 allergic and 3 healthy subjects were analyzed.…”

Section: Immunotransmission Emmentioning

confidence: 99%

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients

Joenväära

Mattila²,

Renkonen

et al. 2009

Journal of Allergy and Clinical Immunology

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Major causes of olfactory disorders are sinonasal disease, viral upper respiratory tract infection, head trauma and old age. Olfactory testing is an important part of objective assesment of the severity of the disease in chronic rhinosinusitis and nasal polyposis. The aim of this study was to correlate results of objective smell testing with subjective scores on olfaction and other nasal symptoms in different subgroups of patients with smell impairment.Data were extracted from questionnaires filled by patients sent to smell testing by the ENT specialist. For the analysis data were divided in subgroups: 20 with chronic rhinosinusitis (CRS), 24 patients operated for nasal polyps, 7 patients with nasal polyps on medical treatment, 7 with hyposmia after common cold, 4 with anosmia and 11 controls with no smell impairment. Smell testing was done by using the Sniffin Sticks 12 complete odorant. This test is based on the assessment of odor identification abilities for 12 standard odors with forced choice. Subjective scores on (0-4) were taken for olfaction, nasal obstruction, hypersecretion and headache.The correlation between subjective score for olfaction and olfactometry score was significant for the whole group (r 0.682), and was similar when anosmic and controls were excluded. Subjective olfaction and olfactometry score did not correlate with any other symptom. Comparing correlation coefficients between the subgroups, it seems that patients with CRS and nonoperated nasal polyp patients have better correlation between subjective and objective smell assesment than patients operated for nasal polyps and those who had olfactory lesion following viral infection.Although correlation between subjective and objective smell assesment is significant, some subgroups of patients overrate their ability to recognize odors. STRESS EFFECTS ON ALLERGIC INFLAMMATION OF THE AIRWAYS Pontus Stierna and Susanna GeorenDepartment of Otorhinolaryngology, Karolinska University Hospital, Stockholm, SwedenWe have used a mouse model to investigate the effects of endogenous GC synthesis and GC receptor inhibition, as well as acute stress, and different doses of exogenous administered GCs on inflammatory cells in different cellular compartments in allergic airway inflammation. including nerve growth factor (NGF) in the airways, during allergic inflammation.First we investigated the effects of endogenous GCs on eosinophilic airway inflammation. Inhibition of GC release with metyrapone (ME) induced an increase of bone marrow eosinophilia and when the ME treatment was combined with a GC receptor antagonist (RU 486) the allergen-induced bone marrow eosinophilia was further enhanced.The second study was focused on the effects of timing of a short acute stress on allergic airway inflammation in upper and lower airways. Short stress applied before an allergen challenge decreased the allergen-induced eosinophilia in bronchoalveolar lavage fluid and lungs and also the inflammation in the nasal tissue. No effects on eosinophilia or inflammation were seen...

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Section: Immunotransmission Emmentioning

confidence: 99%

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients

Joenväära

Mattila²,

Renkonen

et al. 2009

Journal of Allergy and Clinical Immunology

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“…The seven genes relatively up-regulated within the refractory cohort (Table IV) included RABGGTB, encoding a prenyl transeferase with anti-apoptotic properties, and POLE, involved in DNA replication and repair (Miura & Izuta, 2004;Rytkonen et al, 2006).…”

Section: Gene Biologymentioning

confidence: 99%

Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy‐refractory diffuse large B‐cell lymphoma

et al. 2008

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SummaryIn order to identify genes associated with primary chemotherapy‐resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B‐cell lymphoma (DLBCL), stage II–IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy‐nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM‐1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin‐3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.

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“…Moreover, ChIP analysis has revealed that RNAP-II complexes bound to the rDNA locus contain Ser7P-CTD and hypophosphorylated RNAP-II molecules (Figure S3). Different studies have demonstrated that the CTD of RNAP-II interacts with several replication components, such as MCMs and DNA polymerase ε [54], [55]. However, the presence of DNA repair, replication or recombination factors in purified CTD-RNAP-II has been found to depend strongly on the purification strategy employed [54], [56], [57].…”

Section: Discussionmentioning

confidence: 99%

“…Different studies have demonstrated that the CTD of RNAP-II interacts with several replication components, such as MCMs and DNA polymerase ε [54], [55]. However, the presence of DNA repair, replication or recombination factors in purified CTD-RNAP-II has been found to depend strongly on the purification strategy employed [54], [56], [57]. The results presented herein suggest that hypophosphorylated RNAP-II and Ser2P-CTD RNAP-II complexes, but not Ser5P-CTD, interact with Orc1p (Figure 5).…”

Section: Discussionmentioning

confidence: 99%

RNAP-II Molecules Participate in the Anchoring of the ORC to rDNA Replication Origins

Mayán¹

2013

PLoS ONE

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The replication of genomic DNA is limited to a single round per cell cycle. The first component, which recognises and remains bound to origins from recognition until activation and replication elongation, is the origin recognition complex. How origin recognition complex (ORC) proteins remain associated with chromatin throughout the cell cycle is not yet completely understood. Several genome-wide studies have undoubtedly demonstrated that RNA polymerase II (RNAP-II) binding sites overlap with replication origins and with the binding sites of the replication components. RNAP-II is no longer merely associated with transcription elongation. Several reports have demonstrated that RNAP-II molecules affect chromatin structure, transcription, mRNA processing, recombination and DNA repair, among others. Most of these activities have been reported to directly depend on the interaction of proteins with the C-terminal domain (CTD) of RNAP-II. Two-dimensional gels results and ChIP analysis presented herein suggest that stalled RNAP-II molecules bound to the rDNA chromatin participate in the anchoring of ORC proteins to origins during the G1 and S-phases. The results show that in the absence of RNAP-II, Orc1p, Orc2p and Cdc6p do not bind to origins. Moreover, co-immunoprecipitation experiments suggest that Ser2P-CTD and hypophosphorylated RNAP-II interact with Orc1p. In the context of rDNA, cryptic transcription by RNAP-II did not negatively interfere with DNA replication. However, the results indicate that RNAP-II is not necessary to maintain the binding of ORCs to the origins during metaphase. These findings highlight for the first time the potential importance of stalled RNAP-II in the regulation of DNA replication.

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DNA polymerase ε associates with the elongating form of RNA polymerase II and nascent transcripts

Cited by 9 publications

References 72 publications

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients

Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy‐refractory diffuse large B‐cell lymphoma

RNAP-II Molecules Participate in the Anchoring of the ORC to rDNA Replication Origins

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