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Mutants of the Saccharomyces cerevisiae VPS genes CCZ1 and YPT7 are blocked in different stages of sporulation.
No full textThe CCZ1 gene is a member of the class B VPS (vacuolar protein sorting) genes and it is engaged in the last stage of delivery of multiple kinds of cargo to the yeast vacuole. In the process of fusion of the multivesicular body (MVB) with the vacuole, Ccz1p forms a complex with Ypt7p. Both genes are non-essential for vegetative growth, but their deletions cause a complete block in spore formation. The results of this study indicate that ccz1Δ cells initiate the meiotic program, properly proceed through premeiotic DNA replication and through the pairing of homologous chromosomes, but fail to progress through the first meiotic divisions and arrest in prophase I with a single nucleus. The mutant cells are defective in spindle formation as well as in duplication and/or separation of the SPBs. ypt7Δ cells, on the other hand, cannot execute DNA synthesis. We also show that expression of a mutated variant of the YPT7 gene suppresses the sporulation and autophagy defects of ccz1Δ cells to a quantitatively similar level, suggesting that restoration of autophagy in the ccz1Δ strain is sufficient to enable its sporulation
Human RECQL5beta stimulates flap endonuclease 1.
Get PDFHuman RECQL5 is a member of the RecQ helicase family which is implicated in genome maintenance. Five human members of the family have been identified; three of them, BLM, WRN and RECQL4 are associated with elevated cancer risk. RECQL1 and RECQL5 have not been linked to any human disorder yet; cells devoid of RECQL1 and RECQL5 display increased chromosomal instability. Here, we report the physical and functional interaction of the large isomer of RECQL5, RECQL5beta, with the human flap endonuclease 1, FEN1, which plays a critical role in DNA replication, recombination and repair. RECQL5beta dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. Moreover, we show that RECQL5beta and FEN1 interact physically and co-localize in the nucleus in response to DNA damage. Our findings, together with the previous literature on WRN, BLM and RECQL4's stimulation of FEN1, suggests that the ability of RecQ helicases to stimulate FEN1 may be a general feature of this class of enzymes. This could indicate a common role for the RecQ helicases in the processing of oxidative DNA damage
Hydrogen peroxide-mediated induction of the Shiga toxinconverting lambdoid prophage ST2-8624 in Escherichia coli O157:H7
Get PDFShiga toxin-producing Escherichia coli (STEC) may cause bloody diarrhea and
hemorrhagic colitis, with sometimes severe complications. Because genes coding
for Shiga toxins are located on lambdoid prophages, effective toxin production
occurs only after prophage induction. However, although agents that effectively
induce prophage l (a paradigm of the family of lambdoid phages) under
laboratory conditions, such as UV irradiation or DNA replication inhibitors, are
well known, it is unlikely that such factors are present in human intestine infected
with STEC. In this report, we demonstrate that induction of a Shiga toxinconverting
prophage in its host (E. coli O157:H7) occurs not only in the presence
of DNA-interfering antibiotics (mitomycin C and norfloxacin) but also under
conditions of oxidative stress [following treatment with hydrogen peroxide
(H2O2)]. Under these conditions, we observed not only effective prophage
induction but also expression of the reporter gene (replacing the original stx2
gene). In the light of previously published reports, indicating that oxidative stress
conditions might occur during colonization of human intestine by enteric bacteria,
and that neutrophil-produced H2O2 can increase production of the Shiga toxin in
a clinical isolate of STEC, these results suggest that oxidative stress may be one of
the agents responsible for stimulating the pathogenicity determinants of STEC,
leading to induction of Shiga toxin-converting prophages in these bacteria
Mechanisms of RNA Degradation by the Eukaryotic Exosome
Get PDFThe exosome is a multi-subunit protein complex involved in essentially all phenomena associated with RNA metabolism in eukaryotic cells. This review discusses recent discoveries in the fields of biochemistry and structural biology that have shed new light on the mechanisms of RNA recruitment to the catalytic subunits of the exosome
Genistein: a natural isoflavone with a potential for treatment of genetic diseases
Get PDFGenistein [4�,5,7-trihydroxyisoflavone or 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] is a
natural isoflavone occurring in many plants known to possess various biological activities, ranging from
phyto-oestrogenic to antioxidative actions. Recent studies indicated that this isoflavone can also be
considered as a drug for as yet untreatable genetic diseases. In the present review, we discuss a plausible
use of genistein in treatment of two genetic disorders: CF (cystic fibrosis) and MPS (mucopolysaccharidosis).
Although various biological actions of genistein are employed in these two cases, in vitro studies, tests on
animal models and pilot clinical trials suggest that this plant-derived compound might be a real hope for
patients suffering from severe inherited disorders with relatively complicated pathomechanisms, including
those affecting the central nervous system
Low genetic differentiation between two morphotypes of the gastropod <i>Nacella concinna</i> from Admiralty Bay, Antarctica
Get PDFDuring laboratory and field experiments on Nacella concinna on the west coast
of Admiralty Bay, King George Island (Antarctica) clear morphological and behavioural
differences between two limpet forms (N. concinna polaris and N. concinna concinna) were
found. They suggested presence of genetic divergence. AFLP (amplified fragment length
polymorphism) profiling of N. concinna individuals representing the two forms revealed
nearly 32% of polymorphic bands; only 2% of them differed between the forms. Our results
suggest that the observed phenotypic variation seems to be a result of adaptation to environ−
mental conditions and not of any genetic divergence
Związki naturalne w farmacji i medycynie. Kwas salicylowy i fenolokwasy. Natural products in pharmacy and medicine. Salicylic acid and related phenolic acids.
Get PDFKwas salicylowy (KS) jest najprostszym przedstawicielem grupy metabolitów wtórnych roślin wyższych, zwanych fenolokwasami, które odgrywają ważne role biologiczne zarówno w fizjologii roślin, jak i w ochronie zdrowia ludzkiego. W artykule przedstawiono krótki rys historyczny badań i zastosowań KS, pozyskiwanego ze źródeł naturalnych i przemysłowych, oraz wiadomości dotyczące występowania jego analogów strukturalnych w roślinach. Opisano rolę KS jako fitohormonu i induktora odpowiedzi na stres u roślin oraz jako inhibitora wytwarzania mediatorów stanu zapalnego u ludzi.
Salicylic acid (SA) is the simplest example of molecule belonging to the group of plant secondary metabolites, classified as phenolic acids. These compounds are of considerable importance not only for well being of the host organisms but also have advantageous influence on human physiology. Short account of natural and synthetic SA studies, as well as its structural analogs,
is presented. The role of SA in plant local and systemic pathogen resistance phenomena is described, and its significance for anti-inflammatory therapies in humans are discussed
Why similar protein sequences encode similar three-dimensional structures?
Get PDFEvolutionarily related proteins have similar sequences. Such similarity is called homology and can be described using substitution matrices such as Blosum 60. Naturally occurring homologous proteins usually have similar stable tertiary structures and this fact is used in so-called homology modeling. In contrast, the artificial protein designed by the Regan group has 50% identical sequence to the B1 domain of Streptococcal IgG-binding protein and a structure similar to the protein Rop. In this study, we asked the question whether artificial similar protein sequences (pseudohomologs) tend to encode similar protein structures, such as proteins existing in nature. To answer this question, we designed sets of protein sequences (pseudohomologs) homologous to sequences having known three-dimensional structures (template structures), same number of identities, same composition and equal level of homology, according to Blosum 60 substitution matrix as the known natural homolog. We compared the structural features of homologs and pseudohomologs by fitting them to the template structure. The quality of such structures was evaluated by threading potentials. The packing quality was measured using three-dimensional homology models. The packing quality of the models was worse for the “pseudohomologs” than for real homologs. The native homologs have better threading potentials (indicating better sequence-structure fit) in the native structure than the designed sequences. Therefore, we have shown that threading potentials and proper packing are evolutionarily more strongly conserved than sequence homology measured using the Blosum 60 matrix. Our results indicate that three-dimensional protein structure is evolutionarily more conserved than expected due to sequence conservation
SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.
Get PDFN-linked glycosylation is the most frequent modification of secreted and membrane-bound proteins in eukaryotic cells, disruption of which is the basis of the congenital disorders of glycosylation (CDGs). We describe a new type of CDG caused by mutations in the steroid 5a-reductase type 3 (SRD5A3) gene. Patients have mental retardation and ophthalmologic and cerebellar defects. We found that SRD5A3 is necessary for the reduction of the alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide precursor used for N-glycosylation. The presence of residual dolichol in cells depleted for this enzyme suggests the existence of an unexpected alternative pathway for dolichol de novo biosynthesis. Our results thus suggest that SRD5A3 is likely to be the long-sought polyprenol reductase and reveal the genetic basis of one of the earliest steps in protein N-linked glycosylation
