| 1. |
- Alao, John Patrick, 1973-, et al.
(författare)
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Rad3 and Sty1 function in S. pombe: an integrated response to DNA damage and environmental stress?
- 2008
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Ingår i: Molecular Microbiology. ; 68, s. 246-254
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Forskningsöversikt (refereegranskat)abstract
- In Schizosaccharomyces pombe, the Ataxia Telangiectasia-mutated (Atm)/Atm and Rad 3 Related (Atr) homologue Rad3 is an essential regulator of the response to DNA damage and stalled replication forks. Rad3 activates the downstream kinases Chk1 and Cds1. These kinases in turn inhibit cell cycle progression by mediating Cdc2 phosphorylation. Studies in both yeast and mammalian cells suggest additional roles for Rad3 in regulating cellular responses to environmental stress. In S. pombe, cellular responses to various environmental stresses are regulated primarily through the stress-activated MAP kinase p38 homologue Sty1. An important function of Sty1 is to drive cells rapidly through mitosis by facilitating the accumulation of Cdc25. Interestingly, Sty1 is activated simultaneously with Rad3 following exposure to UV radiation or ionizing radiation (IR). Similarly, exposure to environmental stresses induces the expression of rad3+, cds1+ and other checkpoint regulator genes. It is currently unclear how the pathways regulated by Sty1 and Rad3 and their opposing effects on mitosis are integrated. Recent studies suggest that Sty1 and Rad3 function together to regulate the expression of several stress response genes following exposure to IR. In this review, we discuss current knowledge on the interaction of Rad3/Atm and Sty1/p38 in regulating cellular responses to environmental stress and DNA damage.
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| 2. |
- Axelson-Fisk, Marina, et al.
(författare)
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Comparative genomics and gene finding in fungi
- 2006
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Ingår i: Topics in Current Genetics. ; 15, s. 1-28
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Forskningsöversikt (refereegranskat)abstract
- In the spring of 2005, we had access to 18 fully sequenced fungal genomes, and more are coming rapidly. New approaches and methods are being developed to harvest this information source to derive functional predictions and understanding of genome anatomy. Comparative genomics also tells us stories about the evolution of yeasts and filamentous fungi, and the genome rearrangements that marked their history. For example, several genes encoding proteins required for heterochromatin formation and RNA interference have been lost uniformly throughout the Hemiascomycetes, although some genes remain in a few species in a scattered pattern. Being the first eukaryote to have its genome fully sequenced, Saccharomyces cerevisiae was the forerunner for in silico methods of genome annotation in general, and gene finding in particular. Lessons learned from the comparatively simple genome of this budding yeast have paved the way for efficient genome analysis in other fungi as well as eukaryotes in general. Several fungal species are of important applied interest for mankind, and so it is essential to utilise comparative genomics to derive functional information about them. The set of fungal genomes: simple, related in evolution, and with a high density of functional information, can serve as a highly efficient test bed for the further development of comparative genomics.
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| 3. |
- Hult, Malin, 1974-, et al.
(författare)
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SAPK and control of translation
- 2008
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Ingår i: Topics in Current Genetics. ; 20, s. 299-310
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Forskningsöversikt (refereegranskat)abstract
- Posttranscriptional control of translation is essential for rapid adaptation to changing environmental conditions, and also in some instances of hormonal control. General translational control, which affects all mRNAs, can target the initiation or the elongation step. General regulation of initiation commonly targets the translation initiation factors eIF2α or eIF4E; a common target for regulation of elongation is eEF-2. In all these cases, SAPK signalling has been shown to play a role. Posttranscriptional regulation of individual mRNAs is ultimately determined by cis-acting sequences, most famously the ARE sequences. SAPK’s are also implicated in translational control of individual mRNA species through ARE’s and probably other sequence elements. In addition, SAPK signalling can influence the use of alternative translation start sites, and transcription and mRNA stability of components of the protein synthesis machinery. While most knowledge of translational control is derived from mammalian systems, yeast genetics is recently providing complementary understanding.
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| 4. |
- Marín-Navarro, Julia, et al.
(författare)
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Global estimation of mRNA stability in yeast
- 2011
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Ingår i: Methods in Molecular Biology. ; 734, s. 3
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Forskningsöversikt (refereegranskat)abstract
- Turnover of mRNA is an important level of gene regulation. Individual mRNAs have different intrinsic stabilities. Moreover, mRNA stability changes dynamically with conditions such as hormonal stimulation or cellular stress. While accurate methods exist to measure the half-life of an individual transcript, global methods to estimate mRNA turnover have limitations in terms of resolution in time and precision. We describe and compare two complementary approaches to estimating global transcript stability: (1) direct measurement of decay rates; (2) indirect estimation of turnover from determination of mRNA synthesis rates and steady-state levels. Since the two approaches have distinct strengths yet confer different cellular perturbations, it is valuable to consider results obtained with both methods. The practical aspects of the chapter are written from a yeast perspective; the general considerations hold true for all eukaryotes, however.
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| 5. |
- Sunnerhagen, Per, 1959-
(författare)
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Cytoplasmatic post-transcriptional regulation and intracellular signalling
- 2007
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Ingår i: Mol Genet Genomics. ; 277:4, s. 341-55
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Forskningsöversikt (refereegranskat)abstract
- Studies of intracellular signalling have traditionally focused on regulation at the levels of initiation of transcription on one hand, and post-translational regulation on the other. More recently, it is becoming apparent that the post-transcriptional level of gene expression is also subject to regulation by signalling pathways. The emphasis in this review is on short-term regulation of mRNAs at the levels of degradation and frequency of translation. Interplay between the mRNA translation and degradation machineries and mainly the TOR, stress-induced MAP kinase (SAPK), and DNA damage checkpoint pathways is discussed. Since a large fraction of the molecular mechanisms has been dissected using molecular genetics methods in yeast, most of the examples in this review are from budding and fission yeast. Some parallels are drawn to plant and animal cells. This review is intended for those more familiar with intracellular signalling, and who realise that post-transcriptional regulation may be an underemphasised level of signalling output.
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