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Current Genetics

Damián Gatica, Daniel J Klionsky
In this report, we discuss recent discoveries concerning the effects and specificity of different RNA-binding proteins (RBPs) as they pertain to macroautophagy/autophagy. Autophagy is a fundamental cellular degradation and recycling pathway, which has attracted substantial attention because defects in this process are associated with a wide range of human disorders including cancer, neurodegeneration, and metabolic diseases. Autophagy must be tightly controlled-either too much or too little can be deleterious...
February 19, 2019: Current Genetics
Barbara Koch, Ana Traven
Mitochondrial fission shows potential as a therapeutic target in non-infectious human diseases. The compound mdivi-1 was identified as a mitochondrial fission inhibitor that acts against the evolutionarily conserved mitochondrial fission GTPase Dnm1/Drp1, and shows promising data in pre-clinical models of human pathologies. Two recent studies, however, found no evidence that mdivi-1 acts as a mitochondrial fission inhibitor and proposed other mechanisms. In mammalian cells, Bordt et al. showed that mdivi-1 inhibits complex I in mitochondria (Dev Cell 40:583, 2017)...
February 19, 2019: Current Genetics
Michael R Lawson, James M Berger
The bacterial hexameric helicase known as Rho is an archetypal sequence-specific transcription terminator that typically halts the synthesis of a defined set of transcripts, particularly those bearing cytosine-rich 3'-untranslated regions. However, under conditions of translational stress, Rho can also terminate transcription at cytosine-poor sites when assisted by the transcription factor NusG. Recent structural, biochemical, and computational studies of the Rho·NusG interaction in Escherichia coli have helped establish how NusG reprograms Rho activity...
February 9, 2019: Current Genetics
Lenka Senohrabkova, Ivana Malcova, Jiri Hasek
Cells have elaborated a complex strategy to maintain protein homeostasis under physiological as well as stress conditions with the aim to ensure the smooth functioning of vital processes and producing healthy offspring. Impairment of one of the most important processes in living cells, translation, might have serious consequences including various brain disorders in humans. Here, we describe a variant of the translation initiation factor eIF3a, Rpg1-3, mutated in its PCI domain that displays an attenuated translation efficiency and formation of reversible assemblies at physiological growth conditions...
February 4, 2019: Current Genetics
Xinchen Teng, J Marie Hardwick
A critical function of human, yeast, and bacterial cells is the ability to sense and respond to available nutrients such as glucose and amino acids. Cells must also detect declining nutrient levels to adequately prepare for starvation conditions by inhibiting cell growth and activating autophagy. The evolutionarily conserved protein complex TORC1 regulates these cellular responses to nutrients, and in particular to amino acid availability. Recently, we found that yeast Whi2 (Saccharomyces cerevisiae) and a human counterpart, KCTD11, that shares a conserved BTB structural domain, are required to suppress TORC1 activity under low amino acid conditions...
January 30, 2019: Current Genetics
Alexandra Voutsina, George S Fragiadakis, Kalliopi Gkouskou, Despina Alexandraki
To gain insights on the transcriptional switches that modulate proper copper homeostasis in yeast, we have examined in detail functional interactions of the relevant transcriptional activator Mac1. We identified Hir1 transcriptional repressor and histone chaperone as a Mac1-interacting protein. This association directly recruits Hir1 on a Mac1 target, CTR1 promoter, quantitatively under induction conditions. We also found Hir1 interacting directly with a previously unknown partner, the Ssn6 (Cyc8) co-regulator...
January 28, 2019: Current Genetics
Jian Jiao, Shuai Wang, Mingli Liang, Yuhong Zhang, Xinxin Xu, Wei Zhang, Bo Liu
An ideal inducible promoter presents inducibility with an inducer and no basal transcription without inducer. Previous studies have shown that PLRA3 in Pichia pastoris is a strong rhamnose-inducible promoter for driving the industrial production of recombinant proteins. However, another important profile of PLRA3 , the basal transcription, was not investigated yet. In this study, the basal transcription of PLRA3 was assessed according to the profiles of two test strains grown in media lacking rhamnose: (1) the production of secretory β-galactosidase in P...
January 24, 2019: Current Genetics
Natalia García-Blanco, Sergio Moreno
Cell division is regulated by cyclin-dependent kinases (Cdks) and requires the periodic activation and inactivation of transcription factors that generate waves of gene expression in different cell-cycle phases. In fission yeast, the MCB-binding transcription factor (MBF) is activated at the end of G1 and regulates the expression of a set of genes that encode for proteins involved in the G1/S transition and DNA replication. Here, we review the importance of controlling MBF by Cdk activity at the onset of S phase...
January 24, 2019: Current Genetics
Zih-Jie Shen, Spike Postnikoff, Jessica K Tyler
The number of times a cell divides before irreversibly arresting is termed replicative lifespan. Despite discovery of many chemical, dietary and genetic interventions that extend replicative lifespan, usually first discovered in budding yeast and subsequently shown to apply to metazoans, there is still little understanding of the underlying molecular mechanisms involved. One unifying theme is that most, if not all, interventions that extend replicative lifespan induce "hormesis", where a little inflicted damage makes cells more able to resist similar challenges in the future...
January 23, 2019: Current Genetics
Nancy M Hollingsworth, Robert Gaglione
Recombination, along with sister chromatid cohesion, is used during meiosis to physically connect homologous chromosomes so that they can be segregated properly at the first meiotic division. Recombination is initiated by the introduction of programmed double strand breaks (DSBs) into the genome, a subset of which is processed into crossovers. In budding yeast, the regulation of meiotic DSB repair is controlled by a meiosis-specific kinase called Mek1. Mek1 kinase activity promotes recombination between homologs, rather than sister chromatids, as well as the processing of recombination intermediates along a pathway that results in synapsis of homologous chromosomes and the distribution of crossovers throughout the genome...
January 22, 2019: Current Genetics
Lieselotte Vermeersch, Gemma Perez-Samper, Bram Cerulus, Abbas Jariani, Brigida Gallone, Karin Voordeckers, Jan Steensels, Kevin J Verstrepen
When faced with environmental changes, microbes enter a lag phase during which cell growth is arrested, allowing cells to adapt to the new situation. The discovery of the lag phase started the field of gene regulation and led to the unraveling of underlying mechanisms. However, the factors determining the exact duration and dynamics of the lag phase remain largely elusive. Naively, one would expect that cells adapt as quickly as possible, so they can resume growth and compete with other organisms. However, recent studies show that the lag phase can last from several hours up to several days...
January 21, 2019: Current Genetics
Yanxia Zhao, Qun Wang, Shi Wang, Xiaoman Liu, Jae-HyuK Yu, Weifa Zheng, Xiuguo Zhang
The formation of sexual fruiting bodies for plant pathogenic fungi is a key strategy to propagate their progenies upon environmental stresses. Stemphylium eturmiunum is an opportunistic plant pathogen fungus causing blight in onion. This self-fertilizing filamentous ascomycete persists in the soil by forming pseudothecia, the sexual fruiting body which helps the fungus survive in harsh environments. However, the regulatory mechanism of pseudothecial formation remains unknown. To uncover the mechanism for pseudothecial formation so as to find a practical measure to control the propagation of this onion pathogen, we tentatively used DNA methyltransferase inhibitor 5-azacytidine (5-AC) to treat S...
January 16, 2019: Current Genetics
Isabelle Sagot, Damien Laporte
Quiescence is operationally characterized as a temporary and reversible proliferation arrest. There are many preconceived ideas about quiescence, quiescent cells being generally viewed as insignificant sleeping G1 cells. In fact, quiescence is central for organism physiology and its dysregulation involved in many pathologies. The quiescent state encompasses very diverse cellular situations depending on the cell type and its environment. This diversity challenges not only quiescence uniformity but also the universality of the molecular mechanisms beyond quiescence regulation...
January 16, 2019: Current Genetics
Gary P Moran, Matthew Z Anderson, Lawrence C Myers, Derek J Sullivan
Mediator complex has recently emerged as an important regulator of gene expression in pathogenic fungi. Mediator is a multi-subunit complex of polypeptides involved in transcriptional activation in eukaryotes, with roles including preinitiation complex (PIC) assembly and chromatin remodeling. Within the last decade, Mediator has been shown to play an integral role in regulating virulence gene expression and drug resistance in human fungal pathogens. In some fungi, specific Mediator subunits have been shown to be required for virulence...
January 14, 2019: Current Genetics
Héloïse Coutelier, Zhou Xu
Cell proliferation is tightly regulated to avoid propagating DNA damage and mutations, which can lead to pathologies such as cancer. To ensure genome integrity, cells activate the DNA damage checkpoint in response to genotoxic lesions to block cell cycle progression. This surveillance mechanism provides time to repair the damage before resuming cell cycle with an intact genome. When the damage is not repaired, cells can, in some conditions, override the cell cycle arrest and proceed with proliferation, a phenomenon known as adaptation to DNA damage...
January 12, 2019: Current Genetics
Yingzi Yun, Xin Zhou, Shuai Yang, Ya Wen, Haixia You, Yuru Zheng, Justice Norvienyeku, Won-Bo Shim, Zonghua Wang
The soil-borne, asexual fungus Fusarium oxysporum f.sp. lycopersici (Fol) is a causal agent of tomato wilt disease. The infection process of Fol comprises root recognition, adhesion, penetration, colonization of the root cortex and hyphal proliferation within the xylem vessels, which are under the regulation of virulence-involved transcription factors (TFs). In this study, we identified a gene, designated FolCZF1, which encodes a C2 H2 TF in Fol. The homologs of FolCzf1 are also known to affect pathogenicity in F...
January 10, 2019: Current Genetics
Isaac Corcoles-Saez, Kangzhen Dong, Rita S Cha
The ataxia-telangiectasia mutated/ATM and Rad3-related (ATM/ATR) family proteins are evolutionarily conserved serine/threonine kinases best known for their roles in mediating the DNA damage response. Upon activation, ATM/ATR phosphorylate numerous targets to stabilize stalled replication forks, repair damaged DNA, and inhibit cell cycle progression to ensure survival of the cell and safeguard integrity of the genome. Intriguingly, separation of function alleles of the human ATM and MEC1, the budding yeast ATM/ATR, were shown to confer widespread protein aggregation and acute sensitivity to different types of proteotoxic agents including heavy metal, amino acid analogue, and an aggregation-prone peptide derived from the Huntington's disease protein...
January 5, 2019: Current Genetics
Elio A Abbondanzieri, Anne S Meyer
The bacterial cytoplasm, once thought to be a relatively undifferentiated reaction medium, has now been recognized to have extensive microstructure. This microstructure includes bacterial microcompartments, inclusion bodies, granules, and even some membrane-bound vesicles. Several recent papers suggest that bacteria may also organize their cytoplasm using an additional mechanism: phase-separated membraneless organelles, a strategy commonly used by eukaryotes. Phase-separated membraneless organelles such as Cajal bodies, the nucleolus, and stress granules allow proteins to become concentrated in sub-compartments of eukaryotic cells without being surrounded by a barrier to diffusion...
January 2, 2019: Current Genetics
Li Zhang, Lina Wang, Yuancun Liang, Jinfeng Yu
Peroxisomes are indispensable organelles that play critical roles in various biological processes in eukaryotic cells. PEX4, one of the peroxins, is the ubiquitin-conjugating enzyme. To functionally characterize roles of FgPEX4 in the phytopathogenic fungus, Fusarium graminearum, we constructed a deletion mutant of FgPEX4 (ΔPEX4) through homologous recombination. ΔPEX4 displayed reduced mycelial growth, conidiation, and the production of perithecia. ΔPEX4 was defective in pathogenicity and production of the mycotoxin deoxynivalenol (DON)...
January 2, 2019: Current Genetics
Wei Xue, Yajing Yin, Fatima Ismail, Chengcheng Hu, Mi Zhou, Xianhe Cao, Shaojie Li, Xianyun Sun
Azoles are the most widely used antifungals for controlling fungal infections in clinic and agriculture. Fungi can adapt to azole stress by rapidly activating the transcription of a number of genes, and some of these genes can elevate resistance to azoles. We had reported the transcription factor CCG-8 as a new regulator in the adaptation to antifungal azole stress in Neurospora crassa and Fusarium verticillioides. In this study, we further investigate the mechanisms by which CCG-8 promotes fungal adaptation to azole stress using N...
January 2, 2019: Current Genetics
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