| 1. |
- Brown, William R A, et al.
(författare)
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Kinetochore assembly and heterochromatin formation occur autonomously in Schizosaccharomyces pombe.
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 111:5, s. 1903-8
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Tidskriftsartikel (refereegranskat)abstract
- Kinetochores in multicellular eukaryotes are usually associated with heterochromatin. Whether this heterochromatin simply promotes the cohesion necessary for accurate chromosome segregation at cell division or whether it also has a role in kinetochore assembly is unclear. Schizosaccharomyces pombe is an important experimental system for investigating centromere function, but all of the previous work with this species has exploited a single strain or its derivatives. The laboratory strain and most other S. pombe strains contain three chromosomes, but one recently discovered strain, CBS 2777, contains four. We show that the genome of CBS 2777 is related to that of the laboratory strain by a complex chromosome rearrangement. As a result, two of the kinetochores in CBS 2777 contain the central core sequences present in the laboratory strain centromeres, but lack adjacent heterochromatin. The closest block of heterochromatin to these rearranged kinetochores is ∼100 kb away at new telomeres. Despite lacking large amounts of adjacent heterochromatin, the rearranged kinetochores bind CENP-A(Cnp1) and CENP-C(Cnp3) in similar quantities and with similar specificities as those of the laboratory strain. The simplest interpretation of this result is that constitutive kinetochore assembly and heterochromatin formation occur autonomously.
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| 2. |
- Liti, Gianni, et al.
(författare)
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High quality de novo sequencing and assembly of the Saccharomyces arboricolus genome.
- 2013
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Ingår i: BMC genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Comparative genomics is a formidable tool to identify functional elements throughout a genome. In the past ten years, studies in the budding yeast Saccharomyces cerevisiae and a set of closely related species have been instrumental in showing the benefit of analyzing patterns of sequence conservation. Increasing the number of closely related genome sequences makes the comparative genomics approach more powerful and accurate. RESULTS: Here, we report the genome sequence and analysis of Saccharomyces arboricolus, a yeast species recently isolated in China, that is closely related to S. cerevisiae. We obtained high quality de novo sequence and assemblies using a combination of next generation sequencing technologies, established the phylogenetic position of this species and considered its phenotypic profile under multiple environmental conditions in the light of its gene content and phylogeny. CONCLUSIONS: We suggest that the genome of S. arboricolus will be useful in future comparative genomics analysis of the Saccharomyces sensu stricto yeasts.
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| 3. |
- Smith, LK, et al.
(författare)
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Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1100-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selectively controls their transport and translation during adaptation to BRAF-targeted therapy. UHMK1 inactivation induces cell death by disrupting therapy induced metabolic reprogramming, and importantly, delays resistance to BRAF and MEK combination therapy in multiple in vivo models. We propose selective mRNA processing and translation by UHMK1 constitutes a mechanism of non-genetic resistance to targeted therapy in melanoma by controlling metabolic plasticity induced by therapy.
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| 4. |
- Troll, Valentin R., et al.
(författare)
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Crustal CO2 liberation during the 2006 eruption and earthquake events at Merapi volcano, Indonesia
- 2012
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 39, s. L11302-
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Tidskriftsartikel (refereegranskat)abstract
- High-temperature volcanic gas is widely considered to originate from ascending, mantle-derived magma. In volcanic arc systems, crustal inputs to magmatic gases mainly occur via subducted sediments in the mantle source region. Our data from Merapi volcano, Indonesia imply, however, that during the April-October 2006 eruption significant quantities of CO2 were added from shallow crustal sources. We show that prior to the 2006 events, summit fumarole gas delta C-13((CO2)) is virtually constant (delta C-13(1994-2005) = -4.1 +/- 0.3 parts per thousand), but during the 2006 eruption and after the shallow Yogyakarta earthquake of late May, 2006 (M6.4; hypocentres at 10-15 km depth), carbon isotope ratios increased to -2.4 +/- 0.2 parts per thousand. This rise in delta C-13 is consistent with considerable addition of crustal CO2 and coincided with an increase in eruptive intensity by a factor of similar to 3 to 5. We postulate that this shallow crustal volatile input supplemented the mantle-derived volatile flux at Merapi, intensifying and sustaining the 2006 eruption. Late-stage volatile additions from crustal contamination may thus provide a trigger for explosive eruptions independently of conventional magmatic processes.
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