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Showing papers by "Guy-Franck Richard published in 2014"


Journal ArticleDOI
TL;DR: The high-quality genome of this species that diverged early in Saccharomycotina will allow further fundamental studies on comparative genomics, evolution and phylogenetics, and enzymes with biotechnological potential were identified, such as two extracellular tannases of the tannic-acid catabolic route, and a new pathway for the assimilation of n-butanol via butyric aldehyde andbutyric acid.
Abstract: Background: The industrially important yeast Blastobotrys (Arxula) adeninivorans is an asexual hemiascomycete phylogenetically very distant from Saccharomyces cerevisiae. Its unusual metabolic flexibility allows it to use a wide range of carbon and nitrogen sources, while being thermotolerant, xerotolerant and osmotolerant. Results: The sequencing of strain LS3 revealed that the nuclear genome of A. adeninivorans is 11.8 Mb long and consists of four chromosomes with regional centromeres. Its closest sequenced relative is Yarrowia lipolytica, although mean conservation of orthologs is low. With 914 introns within 6116 genes, A. adeninivorans is one of the most intron-rich hemiascomycetes sequenced to date. Several large species-specific families appear to result from multiple rounds of segmental duplications of tandem gene arrays, a novel mechanism not yet described in yeasts. An analysis of the genome and its transcriptome revealed enzymes with biotechnological potential, such as two extracellular tannases (Atan1p and Atan2p) of the tannic-acid catabolic route, and a new pathway for the assimilation of n-butanol via butyric aldehyde and butyric acid. Conclusions: The high-quality genome of this species that diverged early in Saccharomycotina will allow further fundamental studies on comparative genomics, evolution and phylogenetics. Protein components of different pathways for carbon and nitrogen source utilization were identified, which so far has remained unexplored in yeast, offering clues for further biotechnological developments. In the course of identifying alternative microorganisms for biotechnological interest, A. adeninivorans has already proved its strengthened competitiveness as a promising cell factory for many more applications.

68 citations


Journal ArticleDOI
18 Apr 2014-PLOS ONE
TL;DR: It is the first demonstration that induction of a TALEN in an eukaryotic cell leads to shortening of trinucleotide repeat tracts to lengths below pathological thresholds in humans, with 100% efficacy and very high specificity.
Abstract: Trinucleotide repeat expansions are responsible for more than two dozens severe neurological disorders in humans. A double-strand break between two short CAG/CTG trinucleotide repeats was formerly shown to induce a high frequency of repeat contractions in yeast. Here, using a dedicated TALEN, we show that induction of a double-strand break into a CAG/CTG trinucleotide repeat in heterozygous yeast diploid cells results in gene conversion of the repeat tract with near 100% efficacy, deleting the repeat tract. Induction of the same TALEN in homozygous yeast diploids leads to contractions of both repeats to a final length of 3–13 triplets, with 100% efficacy in cells that survived the double-strand breaks. Whole-genome sequencing of surviving yeast cells shows that the TALEN does not increase mutation rate. No other CAG/CTG repeat of the yeast genome showed any length alteration or mutation. No large genomic rearrangement such as aneuploidy, segmental duplication or translocation was detected. It is the first demonstration that induction of a TALEN in an eukaryotic cell leads to shortening of trinucleotide repeat tracts to lengths below pathological thresholds in humans, with 100% efficacy and very high specificity.

57 citations


Journal ArticleDOI
01 May 2014-Yeast
TL;DR: This approach was used to characterize elutriation parameters and S‐phase progression of four yeast species and could theoretically be applied to any culture of single, individual cells.
Abstract: Centrifugal elutriation discriminates cells according to their sedimentation coefficients, generating homogeneous samples well suited for genomic comparative approaches. It can, for instance, isolate G1 daughter cells from a Saccharomyces cerevisiae unsynchronized population, alleviating ageing and cell-cycle biases when conducting genome-wide/single-cell studies. The present report describes a straightforward and robust procedure to determine whether a cell population of virtually any yeast species can be efficiently elutriated, while offering solutions to optimize success. This approach was used to characterize elutriation parameters and S-phase progression of four yeast species (S. cerevisiae, Candida glabrata, Lachancea kluyveri and Pichia sorbitophila) and could theoretically be applied to any culture of single, individual cells.

20 citations


Patent
26 Nov 2014
TL;DR: In this article, the authors present a set of moyens for deletion partielle ou complete d'au moins a repetition ADN en tandem in a double brin structure.
Abstract: La presente demande porte sur des moyens, qui derivent d'effecteurs TAL et de TALEN. La structure desdits moyens est specialement concue pour la deletion partielle ou complete d'au moins une repetition ADN en tandem, plus particulierement pour la deletion partielle ou complete d'au moins une repetition ADN en tandem dans un ADN double brin, plus particulierement pour la deletion partielle ou complete d'au moins une repetition ADN en tandem, qui est contenue dans un ADN double brin et qui forme une structure secondaire complexe, telle qu'une epingle a cheveu, une triple helice ou une structure secondaire tetraplex. Les moyens selon la presente invention sont particulierement utiles dans le traitement et/ou la prevention et/ou les soins palliatifs d'une maladie ou d'un trouble impliquant au moins une repetition ADN en tandem, telle que DM1, SCA8, SCA12, HDL2, SBMA, HD, DRPLA, SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, PSACH, DM2, SCA10, SPD1, OPMD, CCD, HPE5, le syndrome HFG, BPES, EIEE1, FRAXA, FXTAS et FRAXE.

Patent
26 Nov 2014
TL;DR: In this paper, the means of the application are adapted for partial or full deletion of at least one DNA tandem repeat, which is contained in a double-stranded DNA and forms a complex secondary structure, such as a hairpin, a triple helix or a tetraplex secondary structure.
Abstract: The application relates to means, which derive from TAL effectors and TALENs. The structure of the means of the application is especially adapted for partial or full deletion of at least one DNA tandem repeat, more particularly for partial or full deletion of at least one DNA tandem repeat in a double-stranded DNA, more particularly for partial or full deletion of at least one DNA tandem repeat, which is contained in a double-stranded DNA and, which forms a complex secondary structure, such as a hairpin, a triple helix or a tetraplex secondary structure. The means of the application are notably useful in the treatment and/or prevention and/or palliation of a disease or disorder involving at least one DNA tandem repeat, such as DM1, SCA8, SCA12, HDL2, SBMA, HD, DRPLA, SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, PSACH, DM2, SCA10, SPD1, OPMD, CCD, HPE5, HFG syndrome, BPES, EIRE1, FRAXA, FXTAS and FRAXE.