HU protein is a member of nucleoid-associated proteins (NAPs) and is an important regulator of bacterial virulence, pathogenesis and survival. NAPs are mainly DNA structuring proteins that influence several molecular processes by binding the DNA. HU ́s indispensable role in DNA-related processes in bacteria was described. HU protein is a necessary bacterial transcription factor and is considered to be a virulence determinant as well. Less is known about its direct role in host-pathogen interactions. The latest studies suggest that HU protein may be secreted outside bacteria and be a part of the extracellular matrix. Moreover, HU protein can be internalized in a host cell after bacterial infection. Its role in the host cell is not well described and further studies are extremely needed. Existing results suggest the involvement of HU protein in host cell immune response modulation in bacterial favor, which can help pathogens resist host defense mechanisms. A better understanding of the HU protein's role in the host cell will help to effective treatment development.

• MeSH
• bakteriální proteiny * genetika   MeSH
• DNA bakterií metabolismus   MeSH
• DNA vazebné proteiny * metabolismus   MeSH
• DNA chemie   MeSH
• faktory virulence MeSH
• interakce hostitele a patogenu MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Nucleoid-associated proteins belong to a group of small but abundant proteins in bacterial cells. These transcription regulators are responsible for many important cellular processes and also are involved in pathogenesis of bacteria. The best-known nucleoid-associated proteins, such as HU, FIS, H-NS, and IHF, are often discussed. The most important findings in research concerning HU protein are described in this mini review. Its roles in DNA compaction, shape modulation, and negative supercoiling induction have been studied intensively. HU protein regulates bacteria survival, growth, SOS response, virulence genes expression, cell division, and many other cell processes. Elucidating the mechanism of HU protein action has been the subject of many research projects. This mini review provides a comprehensive overview of the HU protein.

• MeSH
• bakteriální proteiny chemie   genetika   metabolismus   MeSH
• DNA bakterií metabolismus   MeSH
• DNA vazebné proteiny chemie   genetika   metabolismus   MeSH
• DNA chemie   MeSH
• posttranslační úpravy proteinů MeSH
• regulace genové exprese u bakterií fyziologie   MeSH
• vazba proteinů MeSH
• virulence genetika   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Mitochondrial nucleoids consist of several different groups of proteins, many of which are involved in essential cellular processes such as the replication, repair and transcription of the mitochondrial genome. The eukaryotic, ATP-dependent protease Lon is found within the central nucleoid region, though little is presently known about its role there. Aside from its association with mitochondrial nucleoids, human Lon also specifically interacts with RNA. Recently, Lon was shown to regulate TFAM, the most abundant mtDNA structural factor in human mitochondria. To determine whether Lon also regulates other mitochondrial nucleoid- or ribosome-associated proteins, we examined the in vitro digestion profiles of the Saccharomyces cerevisiae TFAM functional homologue Abf2, the yeast mtDNA maintenance protein Mgm101, and two human mitochondrial proteins, Twinkle helicase and the large ribosomal subunit protein MrpL32. Degradation of Mgm101 was also verified in vivo in yeast mitochondria. These experiments revealed that all four proteins are actively degraded by Lon, but that three of them are protected from it when bound to a nucleic acid; the Twinkle helicase is not. Such a regulatory mechanism might facilitate dynamic changes to the mitochondrial nucleoid, which are crucial for conducting mitochondrial functions and maintaining mitochondrial homeostasis.

• MeSH
• aktivace enzymů MeSH
• DNA vazebné proteiny metabolismus   MeSH
• lidé MeSH
• mitochondriální DNA metabolismus   MeSH
• mitochondriální proteiny metabolismus   MeSH
• mitochondrie genetika   metabolismus   MeSH
• proteasa La metabolismus   MeSH
• proteolýza MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• substrátová specifita MeSH
• transport proteinů MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The nucleoid-associated HU proteins are small abundant DNA-binding proteins in bacterial cell which play an important role in the initiation of DNA replication, cell division, SOS response, control of gene expression and recombination. HU proteins bind to double stranded DNA non-specifically, but they exhibit high affinity to abnormal DNA structures as four-way junctions, gaps or nicks, which are generated during DNA damage. In many pathogens HU proteins regulate expression of genes involved in metabolism and virulence. Here, we show that the Francisella tularensis subsp. holarctica gene locus FTS_0886 codes for functional HU protein which is essential for full Francisella virulence and its resistance to oxidative stress. Further, our results demonstrate that the recombinant FtHU protein binds to double stranded DNA and protects it against free hydroxyl radicals generated via Fenton's reaction. Eventually, using an iTRAQ approach we identified proteins levels of which are affected by the deletion of hupB, among them for example Francisella pathogenicity island (FPI) proteins. The pleiotropic role of HU protein classifies it as a potential target for the development of therapeutics against tularemia.

• MeSH
• bakteriální proteiny metabolismus   MeSH
• delece genu MeSH
• DNA vazebné proteiny metabolismus   MeSH
• DNA metabolismus   MeSH
• faktory virulence metabolismus   MeSH
• Francisella tularensis růst a vývoj   fyziologie   MeSH
• fyziologický stres MeSH
• oxidační stres MeSH
• stanovení celkové genové exprese MeSH
• vazba proteinů MeSH
• virulence MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The nucleoid-associated protein HU is a common bacterial transcription factor, whose role in pathogenesis and virulence has been described in many bacteria. Our recent studies showed that the HU protein is an indispensable virulence factor in the human pathogenic bacterium Francisella tularensis, a causative agent of tularemia disease, and that this protein can be a key target in tularemia treatment or vaccine development. Here, we show that Francisella HU protein is inhibited by Gp46, a protein of Bacillus subtilis bacteriophage SPO1. We predicted that Gp46 could occupy the F. tularensis HU protein DNA binding site, and subsequently confirmed the ability of Gp46 to abolish the DNA-binding capacity of HU protein. Next, we showed that the growth of Francisella wild-type strain expressing Gp46 in trans corresponded to that of a deletion mutant strain lacking the HU protein. Similarly, the efficiency of intracellular proliferation in mouse macrophages resembled that of the deletion mutant strain, but not that of the wild-type strain. These results, in combination with findings from a recent study on Gp46, enabled us to confirm that Gp46 could be a universal inhibitor of HU proteins among bacterial species.

• Publikační typ
• časopisecké články MeSH

Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators. We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (>48h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity.

• MeSH
• buňky Hep G2 MeSH
• DNA vazebné proteiny metabolismus   MeSH
• doxorubicin MeSH
• ethidium MeSH
• GTP-fosfohydrolasy metabolismus   MeSH
• jaterní mitochondrie metabolismus   MeSH
• lidé MeSH
• mitochondriální DNA metabolismus   MeSH
• mitochondriální proteiny metabolismus   MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• poškození DNA MeSH
• proteiny asociované s mikrotubuly metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• transportní proteiny mitochondriální membrány metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

To study the mechanisms involved in the maintenance of a linear mitochondrial genome we investigated the biochemical properties of the recombination protein Mgm101 from Candida parapsilosis. We show that CpMgm101 complements defects associated with the Saccharomyces cerevisiae mgm101-1(ts) mutation and that it is present in both the nucleus and mitochondrial nucleoids of C. parapsilosis. Unlike its S. cerevisiae counterpart, CpMgm101 is associated with the entire nucleoid population and is able to bind to a broad range of DNA substrates in a non-sequence specific manner. CpMgm101 is also able to catalyze strand annealing and D-loop formation. CpMgm101 forms a roughly C-shaped trimer in solution according to SAXS. Electron microscopy of a complex of CpMgm101 with a model mitochondrial telomere revealed homogeneous, ring-shaped structures at the telomeric single-stranded overhangs. The DNA-binding properties of CpMgm101, together with its DNA recombination properties, suggest that it can play a number of possible roles in the replication of the mitochondrial genome and the maintenance of its telomeres.

• MeSH
• buněčné jádro genetika   metabolismus   MeSH
• Candida genetika   metabolismus   MeSH
• DNA fungální genetika   metabolismus   MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• Escherichia coli genetika   metabolismus   MeSH
• exprese genu MeSH
• genom fungální * MeSH
• genom mitochondriální * MeSH
• homeostáza telomer MeSH
• klonování DNA MeSH
• mitochondriální proteiny genetika   metabolismus   MeSH
• mitochondrie genetika   metabolismus   MeSH
• multimerizace proteinu MeSH
• mutace MeSH
• regulace genové exprese u hub * MeSH
• rekombinace genetická MeSH
• rekombinantní proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• telomery chemie   metabolismus   MeSH
• testy genetické komplementace MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• DNA genetika   MeSH
• genetické jevy MeSH
• genom MeSH
• geny fyziologie   MeSH
• proteiny genetika   MeSH
• RNA genetika   MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika

Matrixmetaloproteinázy (MMP) představují skupinu volně cirkulujících enzymů i transmembránových proteinů se schopností rozrušovat extracelulární hmoty a bazální membrány za fyziologických i patologických podmínek. Tyto enzymy umožňují vznik prostředí vhodného k šíření nádorovému procesu. Zvýšená exprese matrixmetaloproteinázy -1 (MMPl) je spojena s počátečním růstem, s dalším šířením karcinomu a jeho metastazováním. Genový polymorfismus promotoru MMPl částečně reguluje genovou expresi tohoto enzymu. Alela 2G znamená zvýšenou transkripční aktivitu, která může být spojená se zvýšeným rizikem vzniku rakoviny plic. Cílem této analýzy bylo zkoumání vztahu mezi nukleotidovým polymorfismem MMPl a metastazováním plicní rakoviny. Celkem bylo vyšetřeno 154 pacientů, 95 s nemalobuněčnou plicní rakovinou a 59 s malobunečnou formou plicní rakoviny. Podle Časového vztahu ke vzniku metastáz byli všichni pacienti rozděleni do tří skupin. Skupina A představovala synchronní tsoučasně) diagnostikované vzdálené metastázy v době diagnózy plicní rakoviny. Skupina B zahrnovala asynchronní diagnostiku metastáz od 1 do 24 měsíců od doby diagnózy primárního nádoru. Skupina C představovala soubor nemocných bez vzdálených metastáz po dobu 2 let sledování od diagnostiky plicní rakoviny. Alelická četnost IG v metastazujících skupinách A+B byla zjištěna v 54 %; četnost 2G ve 46 %. V nemetastazující skupině C alelická četnost IG alely byla zjištěna v 51,7 % a 2G četnost ve 48,3 % případů. V práci nebylo zjištěno, že by se četnosti alel i genotipů mezi jednotlivými skupinami signifikantně lišila. Navíc je právě v nemetastazující skupině C proti očekávání vyšší zastoupení 2G alely. Polymorfismus 1G/2G v promotoru genu pro MMP-1 se tedy pravděpodobně nepodílí na progresi nádorového onemocnění.

Matrix metalloproteinases (MMP) are freely circulating or transmembraneous proteins capable of disrupting extracellular mass and basal membranes under both physiologicyal and pathological conditions. These enzymes promote an environment favourable to the spreading of tumorous processes. A stronger expression of MMP-1 is associated with the initial growth and subsequent spreading of lung carcinoma £ind its metastasizing. The gene polymorphysm of the MMP-1 promoter in part regulates the gene expression of this enzyme. Allele 2G stands for a higher transcription activity, which may go hand in hand with a higher risk of lung cancer. The purpose of our trial was to investigate the relation of MMP-1 nucleoid polymorphism and of metastasizing lung cancer. We examined 154 patients - 95 presented non-small-cell lung carcinoma, 59 its small-cell form. Patients were divided into three groups according to the onset of metastases. In Group A were distant metastases diagnosed simulaneously with the diagnosis of lung cancer. In Group B were metastases diagnosed 1 to 24 months after the diagnosis of the primary tumour. The patients in Group C were free of distant metastases throughout a two-year follow-up Since the diagnosis of lung carcinoma. The overall frequency of allele IG in the metastasizing groups A and B was 54 %, the frequency of 2G was 46 %. In the metastasis-free group C the frequency of allele IG was 51.7 %, of allele 2G 48.3 %. The trial revealed no significant differences in the frequency of alleles and of genotypes between individual groups. Rather unexpectedly in the metastasis-free group C there was a higher proportion of 2G allelic. Most probably the polymorphism 1G/2G in the promoter gene for MMP-1 is not involved in the progres sion of tumours.

• MeSH
• alely MeSH
• bronchogenní karcinom diagnóza   patologie   sekundární   MeSH
• finanční podpora výzkumu jako téma MeSH
• genotyp MeSH
• lidé MeSH
• matrixové metaloproteinasy diagnostické užití   genetika   krev   MeSH
• nádorové supresorové proteiny fyziologie   MeSH
• nádory plic diagnóza   sekundární   MeSH
• onkogeny fyziologie   MeSH
• polymorfismus genetický MeSH
• receptory růstových faktorů fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

• MeSH
• DNA MeSH
• genetika MeSH
• geny MeSH
• molekulární biologie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika
• biologie