Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
RAS/Cyclic AMP and Transcription Factor Msn2 Regulate Mating and Mating-Type Switching in the Yeast Kluyveromyces lactis
Stockholm University, Faculty of Science, The Wenner-Gren Institute, Developmental Biology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute, Developmental Biology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute, Developmental Biology.
2011 (English)In: Eukaryotic Cell, ISSN 1535-9778, E-ISSN 1535-9786, Vol. 10, no 11, 1545-1552 p.Article in journal (Refereed) Published
Abstract [en]

In response to harsh environmental conditions, ascomycetes produce stress-resistant spores to promote survival. As sporulation requires a diploid DNA content, species with a haploid lifestyle, such as Kluyveromyces lactis, first induce mating in response to stress. In K. lactis, mating and mating-type switching are induced by the DNA-binding protein Mts1. Mts1 expression is known to be upregulated by nutrient limitation, but the mechanism is unknown. We show that a ras2 mutation results in a hyperswitching phenotype. In contrast, strains lacking the phosphodiesterase Pde2 had lower switching rates compared to that of the wild type (WT). As Ras2 promotes cyclic AMP (cAMP) production and Pde2 degrades cAMP, these data suggest that low cAMP levels induce switching. Because the MTS1 regulatory region contains several Msn2 binding sites and Msn2 is a transcription factor that is activated by low cAMP levels, we investigated if Msn2 regulates MTS1 transcription. Consistently with this idea, an msn2 mutant strain displayed lower switching rates than the WT strain. The transcription of MTS1 is highly induced in the ras2 mutant strain. In contrast, an msn2 ras2 double mutant strain displays WT levels of the MTS1 transcript, showing that Msn2 is a critical inducer of MTS1 transcription. Strains lacking Msn2 and Pde2 also exhibit mating defects that can be complemented by the ectopic expression of Mts1. Finally, we show that MTS1 is subjected to negative autoregulation, presumably adding robustness to the mating and switching responses. We suggest a model in which Ras2/cAMP/Msn2 mediates the stress-induced mating and mating-type switching responses in K. lactis.

Place, publisher, year, edition, pages
2011. Vol. 10, no 11, 1545-1552 p.
National Category
Biological Sciences
Research subject
Molecular Bioscience
Identifiers
URN: urn:nbn:se:su:diva-65652DOI: 10.1128/EC.05158-11ISI: 000296723600019PubMedID: 21890818OAI: oai:DiVA.org:su-65652DiVA: diva2:464367
Available from: 2011-12-13 Created: 2011-12-13 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Regulation and mechanism of mating-type switching in Kluyveromyces lactis
Open this publication in new window or tab >>Regulation and mechanism of mating-type switching in Kluyveromyces lactis
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Transposable elements (TEs) have had immense impact on the structure, function and evolution of eukaryotic genomes. The work in this thesis identified Kat1, a novel domesticated DNA transposase of the hAT family in the yeast Kluyveromyces lactis. Kat1 triggers a genome rearrangement that results in a switch of mating type from MATa to MATα. Furthermore, Kat1 acts on sequences that presumably are ancient remnants of a long-lost transposable element. Therefore, Kat1 provides a remarkable example of the intricate relationship between transposable elements and their hosts. We showed that Kat1 generates two DNA double strand breaks (DSBs) in MATa and that the DDE motif and several other conserved amino acid residues are important for Kat1 cleavage activity. DNA hairpins were formed on one end of the DSBs whereas the DNA between the DSBs was joined into a circle. Kat1 was transcriptionally activated by nutrient limitation through the transcription factor Mts1 and negatively regulated by translational frameshifting. In conclusion, Kat1 is a highly regulated domesticated transposase that induces sexual differentiation. 

In another study, we developed an assay to measure switching rates in K. lactis and found that the switching rate was ~6x10-4 events/generation. In a genetic screen for mutations that increased mating-type switching, we found mutations in the RAS1 gene. The small GTPase Ras1 regulates cellular cyclic AMP levels and we demonstrated that Mts1 transcription is regulated by the RAS/cAMP pathway and the transcription factor Msn2. Since Ras activity is regulated by nutrient availability, these data likely explains why nutrient limitation induces mating-type switching.

 

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2015. 62 p.
Keyword
yeast, mating-type switching, DSB, gene conversion, transposable elements, RAS/cAMP pathway, nutrient limitation
National Category
Biological Sciences
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-117671 (URN)978-91-7649-204-8 (ISBN)
Public defence
2015-09-01, William-Olssonsalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)
Opponent
Supervisors
Available from: 2015-06-11 Created: 2015-05-29 Last updated: 2015-06-11Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Rajaei, NaghmehÅström, Stefan U.
By organisation
Developmental Biology
In the same journal
Eukaryotic Cell
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 254 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf