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Hdac yeast

Chin-Chuan Chen, Ju-Sui Huang, Tong-Hong Wang, Chen-Hsin Kuo, Chia-Jen Wang, Shu-Huei Wang, Yann-Lii Leu
Effective DNA repair enables cancer cells to survive DNA damage induced by chemotherapeutic or radiotherapeutic treatments. Therefore, inhibiting DNA repair pathways is a promising therapeutic strategy for increasing the efficacy of such treatments. In this study, we found that dihydrocoumarin (DHC), a flavoring agent, causes deficiencies in double-stand break (DSB) repair and prolonged DNA damage checkpoint recovery in yeast. Following DNA damage, Rad52 recombinase was revealed to be inhibited by DHC, which results in deficiencies in DSB repair and prolonged DNA damage checkpoint recovery...
December 7, 2017: International Journal of Molecular Sciences
Raj Luxmi, Rashmi Garg, Sudhakar Srivastava, Aniruddha P Sane
The SIN3 family of co-repressors is a family of highly conserved eukaryotic repressor proteins that regulates diverse functions in yeasts and animals but remains largely uncharacterized functionally even in plants like Arabidopsis. The sole SIN3 homologue in banana, MaSIN3, was identified as a 1408 amino acids, nuclear localized protein conserved to other SIN3s in the PAH, HID and HCR domains. Interestingly, MaSIN3 over-expression in Arabidopsis mimics a state of reduced ABA responses throughout plant development affecting growth processes such as germination, root growth, stomatal closure and water loss, flowering and senescence...
November 2017: Plant Science: An International Journal of Experimental Plant Biology
K Maeda, M Izawa, Y Nakajima, Q Jin, T Hirose, T Nakamura, H Koshino, K Kanamaru, S Ohsato, T Kamakura, T Kobayashi, M Yoshida, M Kimura
Histone deacetylases (HDACs) play an important role in the regulation of chromatin structure and gene expression. We found that dark pigmentation of Magnaporthe oryzae (anamorph Pyricularia oryzae) ΔMohda1, a mutant strain in which an orthologue of the yeast HDA1 was disrupted by double cross-over homologous recombination, was significantly stimulated in liquid culture. Analysis of metabolites in a ΔMohda1 mutant culture revealed that the accumulation of shunt products of the 1,8-dihydroxynaphthalene melanin and ergosterol pathways were significantly enhanced compared to the wild-type strain...
September 1, 2017: Letters in Applied Microbiology
Zichao Zhai, Ming Tang, Yue Yang, Ming Lu, Wei-Guo Zhu, Tingting Li
Most proteins undergo different kinds of modification after translation. Protein acetylation is one of the most crucial post-translational modifications, which causes direct or indirect impact on various biological activities in vivo. As a member of Class III HDACs, SIRT1 was the closest one to the yeast sir2 and drew most attention, while a small number of known SIRT1 substrates caused difficulties to clarify its function. In this work, we designed a novel computational method to screen SIRT1 substrates based on manually collected data and Support Vector Machines (SVMs)...
July 4, 2017: Scientific Reports
Hyeonju Woo, So Dam Ha, Sung Bae Lee, Stephen Buratowski, TaeSoo Kim
Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation...
April 28, 2017: Experimental & Molecular Medicine
Jing Xie, Sabrina Jenull, Michael Tscherner, Karl Kuchler
Chromatin modifications affect gene regulation in response to environmental stimuli in numerous biological processes. For example, N-acetyl-glucosamine and CO2 induce a morphogenetic conversion between white (W) and opaque (O) cells in MTL (mating-type locus) homozygous and heterozygous ( A: /α) strains of the human fungal pathogen Candida albicans Here, we identify 8 histone-modifying enzymes playing distinct roles in the regulation of W/O switching in MTL homozygous and heterozygous strains. Most strikingly, genetic removal of the paralogous genes RPD3 and RPD31, both of which encode almost identical orthologues of the yeast histone deacetylase (HDAC) Rpd3, reveals opposing roles in W/O switching of MTL A: /α strains...
November 15, 2016: MBio
Jared K Woods, Tahereh Ziafazeli, Blanka Rogina
Histone deacetylase (HDAC) 1 regulates chromatin compaction and gene expression by removing acetyl groups from lysine residues within histones. HDAC1 affects a variety of processes including proliferation, development, metabolism, and cancer. Reduction or inhibition of Rpd3, yeast and fly HDAC1 orthologue, extends longevity. However, the mechanism of rpd3's effects on longevity remains unclear. Here we report an overlap between rpd3 and the Insulin/Insulin-like growth factor signaling (IIS) longevity pathways...
November 14, 2016: Aging
Ingo Bauer, Divyavaradhi Varadarajan, Angelo Pidroni, Silke Gross, Stefan Vergeiner, Birgit Faber, Martin Hermann, Martin Tribus, Gerald Brosch, Stefan Graessle
Histone deacetylases (HDACs) remove acetyl moieties from lysine residues at histone tails and nuclear regulatory proteins and thus significantly impact chromatin remodeling and transcriptional regulation in eukaryotes. In recent years, HDACs of filamentous fungi were found to be decisive regulators of genes involved in pathogenicity and the production of important fungal metabolites such as antibiotics and toxins. Here we present proof that one of these enzymes, the class 1 type HDAC RpdA, is of vital importance for the opportunistic human pathogen Aspergillus fumigatus Recombinant expression of inactivated RpdA shows that loss of catalytic activity is responsible for the lethal phenotype of Aspergillus RpdA null mutants...
November 1, 2016: MBio
Hanna Yang, Chang Seob Kwon, Yoonjung Choi, Daeyoup Lee
Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5' promoter and 3' termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes...
August 5, 2016: Biochemical and Biophysical Research Communications
Nebiyu Abshiru, Roshan Elizabeth Rajan, Alain Verreault, Pierre Thibault
Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on histone and nonhistone substrates. Their activity is generally associated with essential cellular processes such as transcriptional repression and heterochromatin formation. Interestingly, abnormal activity of HDACs has been reported in various types of cancers, which makes them a promising therapeutic target for cancer treatment. In the current study, we aim to understand the mechanisms underlying the function of HDACs using an in-depth quantitative analysis of changes in histone acetylation levels in Schizosaccharomyces pombe (S...
July 1, 2016: Journal of Proteome Research
Yanfang Ye, Lucy Kirkham-McCarthy, Robert S Lahue
Trinucleotide repeats (TNRs) are tandem arrays of three nucleotides that can expand in length to cause at least 17 inherited human diseases. Somatic expansions in patients can occur in differentiated tissues where DNA replication is limited and cannot be a primary source of somatic mutation. Instead, mouse models of TNR diseases have shown that both inherited and somatic expansions can be suppressed by the loss of certain DNA repair factors. It is generally believed that these repair factors cause misprocessing of TNRs, leading to expansions...
July 2016: DNA Repair
Godwin Job, Christiane Brugger, Tao Xu, Brandon R Lowe, Yvan Pfister, Chunxu Qu, Sreenath Shanker, José I Baños Sanz, Janet F Partridge, Thomas Schalch
Nucleosome remodeling and deacetylation (NuRD) complexes are co-transcriptional regulators implicated in differentiation, development, and diseases. Methyl-CpG binding domain (MBD) proteins play an essential role in recruitment of NuRD complexes to their target sites in chromatin. The related SHREC complex in fission yeast drives transcriptional gene silencing in heterochromatin through cooperation with HP1 proteins. How remodeler and histone deacetylase (HDAC) cooperate within NuRD complexes remains unresolved...
April 21, 2016: Molecular Cell
Daniel Buszewicz, Rafał Archacki, Antoni Palusiński, Maciej Kotliński, Anna Fogtman, Roksana Iwanicka-Nowicka, Katarzyna Sosnowska, Jan Kuciński, Piotr Pupel, Jacek Olędzki, Michał Dadlez, Aleksandra Misicka, Andrzej Jerzmanowski, Marta Kamila Koblowska
Studies in yeast and animals have revealed that histone deacetylases (HDACs) often act as components of multiprotein complexes, including chromatin remodelling complexes (CRCs). However, interactions between HDACs and CRCs in plants have yet to be demonstrated. Here, we present evidence for the interaction between Arabidopsis HD2C deacetylase and a BRM-containing SWI/SNF CRC. Moreover, we reveal a novel function of HD2C as a regulator of the heat stress response. HD2C transcript levels were strongly induced in plants subjected to heat treatment, and the expression of selected heat-responsive genes was up-regulated in heat-stressed hd2c mutant, suggesting that HD2C acts to down-regulate heat-activated genes...
October 2016: Plant, Cell & Environment
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
AMP-activated protein kinase (AMPK) and its yeast homolog, Snf1, are critical regulators in the maintenance of energy metabolic balance not only stimulating energy production but also inhibiting energy-consuming processes. The AMPK/Snf1 signaling controls energy metabolism by specific phosphorylation of many metabolic enzymes and transcription factors, enhancing or suppressing their functions. The AMPK/Snf1 complexes can be translocated from cytoplasm into nuclei where they are involved in the regulation of transcription...
2016: Cellular Signalling
Yeong Keng Yoon, Chern Ein Oon
The role of sirtuins in age-related diseases is an area of rapidly expanding investigation. Sirtuins are NAD+ -dependent class III histone deacetylases (HDACs) that share extensive homologies with the yeast HDAC Sir2. Class I and class II HDACs inhibitors have been identified as potential anticancer agents and are in clinical studies, but much less is known about class III HDAC inhibitors. However, inhibitors of sirtuins are currently being targeted as potential therapeutic agents for disease such as cancer, neurodegenerative disease and other disorders as sirtuins are discovered to regulate numerous downstream enzymes...
March 10, 2016: Anti-cancer Agents in Medicinal Chemistry
Jeremy Worley, Arron Sullivan, Xiangxia Luo, Matthew E Kaplan, Andrew P Capaldi
The Target of Rapamycin kinase Complex I (TORC1) is a master regulator of cell growth and metabolism in eukaryotes. Studies in yeast and human cells have shown that nitrogen/amino acid starvation signals act through Npr2/Npr3 and the small GTPases Gtr1/Gtr2 (Rags in humans) to inhibit TORC1. However, it is unclear how other stress and starvation stimuli inhibit TORC1, and/or act in parallel with the TORC1 pathway, to control cell growth. To help answer these questions, we developed a novel automated pipeline and used it to measure the expression of a TORC1-dependent ribosome biogenesis gene (NSR1) during osmotic stress in 4700 Saccharomyces cerevisiae strains from the yeast knock-out collection...
December 17, 2015: G3: Genes—Genomes—Genetics
Anuja A George, Nancy C Walworth
Accurate chromosome segregation is necessary to ensure genomic integrity. Segregation depends on the proper functioning of the centromere, kinetochore, and mitotic spindle microtubules and is monitored by the spindle assembly checkpoint (SAC). In the fission yeast Schizosaccharomyces pombe, defects in Dis1, a microtubule-associated protein that influences microtubule dynamics, lead to mitotic arrest as a result of an active SAC and consequent failure to grow at low temperature. In a mutant dis1 background (dis1-288), loss of function of Msc1, a fission yeast homolog of the KDM5 family of proteins, suppresses the growth defect and promotes normal mitosis...
December 2015: Genetics
Sorabh Sharma, Rajeev Taliyan
Huntington's disease (HD) is a progressive neurological disorder for which there are no disease-modifying treatments. Although, the exact underlying mechanism(s) leading to the neural cell death in HD still remains elusive, the transcriptional dysregulation is a major molecular feature. Recently, the transcriptional activation and repression regulated by chromatin acetylation has been found to be impaired in HD pathology. The acetylation and deacetylation of histone proteins is carried out by opposing actions of histone acetyl-transferases and histone deacetylases (HDACs), respectively...
October 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Shouji Matsushima, Junichi Sadoshima
Modification of histones is one of the important mechanisms of epigenetics, in which genetic control is determined by factors other than an individual's DNA sequence. Sirtuin family proteins, which are class III histone deacetylases, were originally identified as gene silencers that affect the mating type of yeast, leading to the name "silent mating-type information regulation 2" (SIR2). They are characterized by their requirement of nicotinamide adenine dinucleotide for their enzyme activity, unlike other classes of histone deacetylases...
November 2015: American Journal of Physiology. Heart and Circulatory Physiology
Shu-Huei Wang, Pei-Ya Lin, Ya-Chen Chiu, Ju-Sui Huang, Yi-Tsen Kuo, Jen-Chine Wu, Chin-Chuan Chen
Chemo- and radiotherapy cause multiple forms of DNA damage and lead to the death of cancer cells. Inhibitors of the DNA damage response are candidate drugs for use in combination therapies to increase the efficacy of such treatments. In this study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA damage by counteracting the DNA damage response. Following DNA damage, the Mec1-dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded by curcumin, which results in deficiencies in double-stand break repair...
2015: PloS One
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