| 1. |
- Kim, Hye-Kyung, 1970, et al.
(författare)
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ADP Stabilizes the Human Rad51-single stranded DNA Complex and Promotes Its DNA Annealing Activity
- 2002
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Ingår i: Genes to Cells. - : Wiley. - 1356-9597 .- 1365-2443. ; 7:11, s. 1125-1134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human Rad51 protein (HsRad51) is a homologue of Escherichia coli RecA protein, and involved in homologous recombination. These eukaryotic and bacterial proteins catalyse strand exchange between two homologous DNA molecules, each forming a complex with single-stranded DNA (ssDNA) and ATP as the initial step. Both proteins hydrolyse ATP; however, the role of ATP hydrolysis appears to vary between the two proteins.Results: Measurements using the fluorescence ssDNA analogue, poly(1,N (6) -etheno-deoxyadenosine), indicate that ATP affects the HsRad51-ssDNA complex, promoting two conformational states: one transient, rather rigid transition state and a final more flexible state. While ADP lowers the affinity of RecA protein to ssDNA, it is found to rather stabilize the HsRad51-ssDNA complex. ADP does not activate the strand exchange by HsRad51 but instead stimulates annealing between complementary ssDNAs.Conclusions: The hydrolysis of ATP promotes a transition of the HsRad51-ssDNA complex from a stiff state to less stiff state. The first state may be important for the strand separation of dsDNA in the initial step of strand exchange, while the second state may be important for annealing in the next step. However, hydrolysis does not dissociate HsRad51 from DNA as a component step of its recycling.
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| 2. |
- Aksenova, Anna, et al.
(författare)
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The HAL3-PPZ1 dependent regulation of nonsense suppression efficiency in yeast and its influence on manifestation of the yeast prion-like determinant [ISP(+)].
- 2007
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Ingår i: Genes to Cells. - : Wiley. - 1356-9597 .- 1365-2443. ; 12:4, s. 435-546
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Tidskriftsartikel (refereegranskat)abstract
- The efficiency of stop codons read-through in yeast is controlled by multiple interactions of genetic and epigenetic factors. In this study, we demonstrate the participation of the Hal3-Ppz1 protein complex in regulation of read-through efficiency and manifestation of non-Mendelian anti-suppressor determinant [ISP(+)]. Over-expression of HAL3 in [ISP(+)] strain causes nonsense suppression, whereas its inactivation displays as anti-suppression of sup35 mutation in [isp(-)] strain. [ISP(+)] strains carrying hal3Delta deletion cannot be cured from [ISP(+)] in the presence of GuHCl. Since Hal3p is a negative regulatory subunit of Ppz1 protein phosphatase, consequences of PPZ1 over-expression and deletion are opposite to those of HAL3. The observed effects are mediated by the catalytic function of Ppz1 and are probably related to the participation of Ppz1 in regulation of eEF1Balpha elongation factor activity. Importantly, [ISP(+)] status of yeast strains is determined by fluctuation in Hal3p level, since [ISP(+)] strains have less Hal3p than their [isp(-)] derivatives obtained by GuHCl treatment. A model considering epigenetic (possibly prion) regulation of Hal3p amount as a mechanism underlying [ISP(+)] status of yeast cell is suggested.
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| 3. |
- Harari-Steinberg, Orit, et al.
(författare)
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COP9 signalosome subunit 5 (CSN5/Jab1) regulates the development of the Drosophila immune system: effects on Cactus, Dorsal and hematopoiesis
- 2007
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Ingår i: Genes to Cells. - : Wiley. - 1356-9597 .- 1365-2443. ; 12, s. 183-195
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Tidskriftsartikel (refereegranskat)abstract
- The COP9 signalosome is a multifunctional regulator essential for Drosophila development. A loss-of-function mutant in Drosophila COP9 signalosome subunit 5 (CSN5) develops melanotic bodies, a phenotype common to mutants in immune signaling. csn5(null) larvae accumulated high levels of Cactus that co-localizes with Dorsal to the nucleus. However, Dorsal-dependent transcriptional activity remained repressed in the absence of an inducing signal, despite its nuclear localization. Dorsal activity in mutant larvae and NFkappaB activity in CSN5 down-regulated mammalian cells can be induced following activation of the Toll/IL-1 pathway. csn5(null) larvae contained more hemocytes than wild-type (wt) larvae. A large portion of these cells have differentiated to lamellocytes (LM), a hemocyte cell type rarely seen in normal larvae. The results presented here indicate that CSN5 is a negative regulator of Dorsal subcellular localization, and of hemocyte proliferation and differentiation. These results further indicate that nuclear localization of Dorsal can be uncoupled from its activation. Surprisingly, CSN5 is not necessary for immune-induced degradation of Cactus.
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| 4. |
- Kahata, Kaoru, et al.
(författare)
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Regulation of transforming growth factor-beta and bone morphogenetic protein signalling by transcriptional coactivator GCN5
- 2004
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Ingår i: Genes to Cells. - : Wiley. - 1356-9597 .- 1365-2443. ; 9:2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Smad proteins are intracellular signalling mediators of transforming growth factor-beta (TGF-beta) superfamily. In the nucleus, activated Smad complexes regulate transcriptional responses of the target genes in cooperation with transcriptional coactivators and corepressors. To identify new components of transcriptional complexes containing Smad proteins, we purified DNA-binding proteins from human breast cancer MCF-7 cell nuclear extract using a Smad-binding DNA element as bait, and identified a coactivator GCN5 as a direct partner of activated Smad complexes. GCN5 is structurally similar to PCAF, which was previously identified as a coactivator for receptor-regulated Smads (R-Smads) for TGF-beta signalling pathways. GCN5 functions like PCAF, in that it binds to TGF-beta-specific R-Smads, and enhances transcriptional activity induced by TGF-beta. In addition, GCN5, but not PCAF, interacts with R-Smads for bone morphogenetic protein (BMP) signalling pathways, and enhances BMP-induced transcriptional activity, suggesting that GCN5 and PCAF have distinct physiological functions in vivo. Moreover, silencing of the GCN5 gene by RNA interference results in repression of transcriptional activities induced by TGF-beta. In conclusion we identified GCN5 as a Smad-binding transcriptional coactivator which positively regulates both TGF-beta and BMP signalling pathways.
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| 5. |
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| 6. |
- Sadek, C. M., et al.
(författare)
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Sptrx-2, a fusion protein composed of one thioredoxin and three tandemly repeated NDP-kinase domains is expressed in human testis germ cells
- 2001
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Ingår i: Genes to Cells. - : Wiley-Blackwell. - 1356-9597 .- 1365-2443. ; 6:12, s. 1077-1090
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Thioredoxins (Trx) are small redox proteins that function as general protein disulphide reductases and regulate several cellular processes such as transcription factor DNA binding activity, apoptosis and DNA synthesis. In mammalian organisms, thioredoxins are generally ubiquitously expressed in all tissues, with the exception of Sptrx-1 which is specifically expressed in sperm cells.RESULTS: We report here the identification and characterization of a novel member of the thioredoxin family, the second with a tissue-specific distribution in human sperm, termed Sptrx-2. The Sptrx-2 ORF (open reading frame) encodes for a protein of 588 amino acids with two different domains: an N-terminal thioredoxin domain encompassing the first 105 residues and a C-terminal domain composed of three repeats of a NDP kinase domain. The Sptrx-2 gene spans about 51 kb organized in 17 exons and maps at locus 7p13-14. Sptrx-2 mRNA is exclusively expressed in human testis, mainly in primary spermatocytes, while Sptrx-2 protein expression is detected from the pachytene spermatocytes stage onwards, peaking at round spermatids stage. Recombinant full-length Sptrx-2 expressed in bacteria displayed neither thioredoxin nor NDP kinase enzymatic activity.CONCLUSIONS: The sperm specific expression of Sptrx-2, together with its chromosomal assignment to a position reported as a potential locus for flagellar anomalies and male infertility phenotypes such as primary ciliary dyskinesia, suggests that it might be a novel component of the human sperm axonemal organization.
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| 9. |
- Bianco, Michele, et al.
(författare)
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The impact of inhomogeneous subgrid clumping on cosmic reionization - II. Modelling stochasticity
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 504:2, s. 2443-2460
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Tidskriftsartikel (refereegranskat)abstract
- Small-scale density fluctuations can significantly affect reionization, but are typically modelled quite crudely. Unresolved fluctuations in numerical simulations and analytical calculations are included using a gas clumping factor, typically assumed to be independent of the local environment. In Paper I, we presented an improved, local density-dependent model for the sub-grid gas clumping. Here, we extend this using an empirical stochastic model based on the results from high-resolution numerical simulations which fully resolve all relevant fluctuations. Our model reproduces well both the mean density-clumping relation and its scatter. We applied our stochastic model, along with the mean clumping one and the Paper I deterministic model, to create large-volume realizations of the clumping field, and used these in radiative transfer simulations of cosmic reionization. Our results show that the simplistic mean clumping model delays reionization compared to local density-dependent models, despite producing fewer recombinations overall. This is due to the very different spatial distribution of clumping, resulting in much higher photoionization rates in the latter cases. The mean clumping model produces smaller H II regions throughout most of reionization, but those percolate faster at late times. It also causes a significant delay in the 21-cm fluctuations peak and yields lower non-Gaussianity and many fewer bright pixels in the PDF distribution. The stochastic density-dependent model shows relatively minor differences from the deterministic one, mostly concentrated around overlap, where it significantly suppresses the 21-cm fluctuations, and at the bright tail of the 21-cm PDFs, where it produces noticeably more bright pixels.
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| 10. |
- Suemnig, A., et al.
(författare)
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Motivational factors for blood donation in first-time donors and repeat donors : a cross-sectional study in West Pomerania
- 2017
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Ingår i: Transfusion Medicine. - : Wiley. - 0958-7578 .- 1365-3148. ; 27:6, s. 413-420
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study aimed to analyse motivational factors for blood donation in different donor groups.BACKGROUND: As the demographic change will result in a decrease of the population in age groups of blood donors, the risk of blood product shortage increases.METHODS: During a 12-month period, every sixth blood donor presenting at the blood donation centre of the University Hospital was asked to complete a self-administered questionnaire assessing motivational factors for blood donation. Despite the formalised enrolment protocol, frequent donors were over-represented in the study cohort, which was adjusted by weighting donors with different numbers of donations per year in such a way that the distribution of numbers of donations per year was the same in the sample as in the donor population.RESULTS: Of 2443 participants, 14·3% were first-time and 85·3% repeat donors. To "help other people" (>90%) and receiving "medical assessment of my blood values" (63-69%) were the strongest motivational factors in all donor groups. Receiving remuneration (49·2% vs 38·1%) was more important for repeat donors than for first-time donors, whereas it was the opposite for "being taken by a friend to the donor clinic" (47·0% vs 15·5%). A potentially important observation is that 33·9% of frequent donors reported feeling physically better after blood donation compared to infrequent donors (29·5%).CONCLUSION: Identification of motivational factors can lead to the design of targeted motivation campaigns for blood donation. The underlying cause of the perceived well-being after blood donation requires further studies.
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