A5022849727- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Fungal and yeast genetics research
- RNA Research and Splicing
- Lipid metabolism and biosynthesis
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Microbial Metabolic Engineering and Bioproduction
- Plant Molecular Biology Research
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Heat shock proteins research
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Molecular Biology Techniques and Applications
- Pancreatic function and diabetes
- Plant Reproductive Biology
- Histone Deacetylase Inhibitors Research
- Gene Regulatory Network Analysis
- Bacterial Genetics and Biotechnology
- Enzyme Catalysis and Immobilization
- Biofuel production and bioconversion
- Receptor Mechanisms and Signaling
- Photosynthetic Processes and Mechanisms
- Microtubule and mitosis dynamics
Ludwig-Maximilians-Universität München
2018-2024
LMU Klinikum
2019
Urologische Klinik München
2018-2019
University of Toronto
2010-2016
The Francis Crick Institute
2016
Donnelly College
2011
University of Graz
2005-2009
We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and 350,000 positive interactions. This comprehensive maps interactions essential gene pairs, highlighting genes as densely connected hubs. Genetic profiles enabled assembly of hierarchical model cell function, including modules corresponding to protein complexes pathways, biological processes, cellular compartments. Negative...
The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished still poorly understood. Using purified yeast replication proteins fully chromatinized templates, we have reconstituted process in vitro. We show that enforces DNA origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently the context chromatin, but subsequent replisome progression histone chaperone FACT (facilitates transcription)....
The dimorphic switch from a single-cell budding yeast to filamentous form enables Saccharomyces cerevisiae forage for nutrients and the opportunistic pathogen Candida albicans invade human tissues evade immune system. We constructed genome-wide set of targeted deletion alleles introduced them into S. strain, Σ1278b. identified genes involved in morphologically distinct forms filamentation: haploid invasive growth, biofilm formation, diploid pseudohyphal growth. Unique appear underlie each...
Storage and degradation of triglycerides are essential processes to ensure energy homeostasis availability precursors for membrane lipid synthesis. Recent evidence suggests that an emerging class enzymes containing a conserved patatin domain centrally important players in degradation. Here we describe the identification characterization major triglyceride lipase adipose lipase/Brummer family, Tgl4, yeast Saccharomyces cerevisiae. Elimination Tgl4 tgl3 background led fat yeast, rendering...
Pioneer transcription factors (pTFs) bind to target sites within compact chromatin, initiating chromatin remodeling and controlling the recruitment of downstream factors. The mechanisms by which pTFs overcome barrier are not well understood. Here, we reveal, using single-molecule fluorescence, how yeast factor Rap1 invades remodels chromatin. Using a reconstituted system replicating promoter architecture, demonstrate that can nucleosomal DNA fiber but with shortened dwell times compared...
Abstract Chromosome replication depends on efficient removal of nucleosomes by accessory factors to ensure rapid access genomic information. Here, we show this process requires recruitment the nucleosome reorganization activity histone chaperone FACT. Using single-molecule FRET, demonstrate that nucleosomal DNA FACT coordinated engagement middle and C-terminal domains Spt16 Pob3 but does not require N-terminus Spt16. structure-guided pulldowns, instead N-terminal region is critical for fork...
BAR domains are protein modules that bind to membranes and promote membrane curvature. One type of domain, the N-BAR contains an additional N-terminal amphipathic helix, which contributes membrane-binding bending activities. The only known N-BAR-domain proteins in budding yeast Saccharomyces cerevisiae, Rvs161 Rvs167, required for endocytosis. We have explored mechanism function endocytosis process using a combined biochemical genetic approach. show purified Rvs161-Rvs167 complex binds...
We describe the Yeast Kinase Interaction Database (KID, http://www.moseslab.csb.utoronto.ca/KID/ ), which contains high- and low-throughput data relevant to phosphorylation events. KID includes 6,225 21,990 high-throughput interactions, from greater than 35,000 experiments. By quantitatively integrating these data, we identified 517 high-confidence kinase-substrate pairs that consider a gold standard. show this standard can be used assess published datasets, suggesting it will enable similar...
Triacylglycerol metabolism in Saccharomyces cerevisiae was analyzed quantitatively using a systems biological approach. Cellular growth, glucose uptake and ethanol secretion were measured as function of time used input for dynamic flux-balance model. By combining mass balances key metabolites with detailed steady-state analysis, we trained model network simulated the time-dependent degradation cellular triacylglycerol its interaction fatty acid membrane lipid synthesis. This approach...
The cell cycle-regulated expression of core histone genes is required for DNA replication and proper cycle progression in eukaryotic cells. Although some factors involved gene transcription are known, the molecular mechanisms that ensure induction during S phase remain enigmatic. Here we demonstrate S-phase model HTA1 yeast regulated by a novel attach-release mechanism involving phosphorylation conserved chromatin boundary protein Yta7 both cyclin-dependent kinase 1 (Cdk1) casein 2 (CK2)....
Significance DNA replication and histone gene transcription are tightly linked occur during the S phase of eukaryotic cell cycle. Histone production outside is highly toxic, underscoring importance regulatory pathways that control expression. Although various regulators have been discovered, molecular mechanisms responsible for spatial temporal expression remained elusive. Here, we describe discovery Spt21 as a long-elusive cycle oscillator restricting to We show here Spt21, together with...
Rtt109 is a fungal histone acetyltransferase (HAT) that catalyzes H3 acetylation functionally associated with chromatin assembly. Rtt109-mediated involves two chaperones, Asf1 and Vps75. In vivo, requires both chaperones for lysine 9 (H3K9ac) but only full H3K56ac. vitro, Rtt109-Vps75 H3K9ac H3K56ac, whereas Rtt109-Asf1 this study, we extend the in vitro chaperone-associated substrate specificity of by showing it acetylates vertebrate linker presence Vps75 not Asf1. addition, demonstrate...
<p>The Hif1 protein in the yeast Saccharomyces cerevisie is an evolutionarily conserved H3/H4-specific chaperone and a subunit of nuclear Hat1 complex that catalyzes acetylation newly synthesized histone H4. Hif1, as well its human homolog NASP, has been implicated array chromatin-related processes including H3/H4 transport, chromatin assembly DNA repair. In this study, we elucidate functional aspects Hif1. Initially establish wide distribution homologs with pattern four...
Abstract The use of synthetic chemicals to selectively interfere with chromatin and the chromatin-bound proteome represents a great opportunity for pharmacological intervention. Recently, foldamers that mimic charge surface double-stranded DNA have been shown selected protein–DNA interactions. However, better understand their potential improve specificity selectivity, effect these molecules on complex needs be investigated. We therefore systematically studied influence using an in vitro...
Abstract The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which a major driver cancer. Yet how chromatin made accessible eukaryotic DNA synthesis poorly understood. Here, we report the characterization remodeling enzyme—Yta7—entirely distinct from classical SNF2-ATPase family remodelers. Yta7 AAA + -ATPase that assembles into ~1 MDa hexameric complexes capable segregating histones DNA....
Abstract The Hif1 protein in the yeast Saccharomyces cerevisie is an evolutionarily conserved H3/H4-specific chaperone and a subunit of nuclear Hat1 complex that catalyzes acetylation newly synthesized histone H4. Hif1, as well its human homolog NASP, has been implicated array chromatin-related processes including H3/H4 transport, chromatin assembly DNA repair. In this study, we elucidate functional aspects Hif1. Initially establish wide distribution homologs with pattern four...
In Saccharomyces cerevisiae , the forkhead (Fkh) transcription factor Fkh1 (forkhead homolog) enhances activity of many DNA replication origins that act in early S-phase (early origins). Current models posit acts directly to promote these origins’ by binding origin-adjacent sites (FKH sites). However, post-DNA functions uses origin are poorly understood. contains a conserved FHA associated) domain, protein-binding module with specificity for phosphothreonine (pT)-containing partner proteins....
We have recently revealed the existence of a cell cycle-regulated chromatin segregase, Yta7 (Yeast Tat-binding Analog 7), involved in chromosome replication. Phosphorylation by S-CDK (S-phase Cyclin-Dependent Kinase) regulates its function. These findings link cycle to biology and suggest how chromatin-modifying enzymes become S phase-specific.
Fun30 is the prototype of Fun30-SMARCAD1-ETL subfamily nucleosome remodelers involved in DNA repair and gene silencing. These proteins appear to act as single-subunit remodelers, but their molecular mechanisms are, at this point, poorly understood. Using multiple sequence alignment structure prediction, we identify an evolutionarily conserved domain that modeled contain a SAM-like fold with one long, protruding helix, which term SAM-key. Deletion SAM-key within budding yeast leads defect...
Abstract In Saccharomyces cerevisiae , the forkhead (Fkh) transcription factor Fkh1 (forkhead homolog) enhances activity of many DNA replication origins that act in early S-phase (early origins). Current models posit acts directly to promote these origins’ by binding origin-adjacent sites (FKH sites). However, post-DNA functions uses origin are poorly understood. contains a conserved FHA associated) domain, protein-binding module with specificity for phosphothreonine (pT)-containing partner...