National Repository of Grey Literature 18 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
Biogenesis and function of nuclear iron-sulfur proteins
Panova, Ekaterina ; Benda, Martin (advisor) ; Smutná, Tamara (referee)
Iron-sulfur clusters are important inorganic cofactors of many cellular reactions, including those that occur in the nucleus. Nuclear iron-sulfur proteins play an important role in DNA replication, genome repair, and maintenance of genome stability. The biosynthesis of these iron-sulfur clusters is initiated in the mitochondria by the iron-sulfur cluster assembly pathway (ISC), continues in the cytosol by the cytosolic iron-sulfur cluster assembly pathway (CIA), and ends with the incorporation of the clusters into target apoproteins such as polymerases, primases, helicases, endonucleases, or glycosylases. This bachelor thesis summarizes current knowledge about the pathways of iron-sulfur cluster biosynthesis, the functions of nuclear iron-sulfur proteins, and the role of the clusters in these proteins, including the phenotypes and clinical manifestations caused by the absence of iron-sulfur clusters. Keywords: iron-sulfur clusters, metalloproteins, nucleus, DNA replication, DNA repair
Role of yeast WSS1 protease in DNA repair.
Adámek, Michael ; Grantz Šašková, Klára (advisor) ; Čáp, Michal (referee)
Sustaining the integrity of DNA throughout the lifetime is critical for every living organism. Therefore organisms evolved numerous ways to detect and repair different types of DNA damage caused by various endogenous and exogenous factors resulting in replication stress. Defects in these repair mechanisms can lead to severe human diseases such as neurological disorders, familial cancers or developmental syndromes. In presented master thesis, we investigated the function of a yeast protein named Wss1, a metalloprotease that participates in a recently discovered DNA repair pathway that proteolytically removes DNA-protein crosslinks. Wss1 shows strong negative interaction with another DNA repair protease, Ddi1, in which case was discovered, that double-deleted yeast strain lacking WSS1 and DDI1 is hypersensitive to hydroxyurea. Hydroxurea is a ribonucleotide reductase inhibitor that, in the end, arrests cells in the S-phase of cell-cycle. Based on previous studies, we performed rescue experiments with various deletions and single-site mutants of Wss1p to assess the involvement of particular yeast Wss1p domains in the replication stress response to hudroxyurea.
Implication of eukaryotic DNA repair machinery in viral replication
Hron, Tomáš ; Španielová, Hana (advisor) ; Harant, Karel (referee)
Eukaryotic DNA damage response is an important mechanism which ensures genome stability. Its components are also mobilized during viral infection as a reaction against extraneous nucleic acid. Additionally, DNA repair machinery seems to be activated by some viruses purposely to provide their replication. This activation is mediated mainly by viral proteins which are able to interact with cellular factors. In many cases, key components of DNA damage mechanisms are associated with viral replication centre and likely participate in this process. Furthermore, cellular DNA damage signaling is exploited to provide competent environment for viral reproduction. However, particular mechanisms how these cellular factors participate in viral infection are still largely unclear. In this thesis, the principles of relationship between viral infection and eukaryotic DNA damage response are summarized and main viral families which are known to activate and utilize these mechanisms for its genom replication are described.
Posttranslational modification of the adapter protein DAXX in the cellular response to genotoxic stress
Bražina, Jan ; Anděra, Ladislav (advisor) ; Černý, Jan (referee) ; Vodička, Pavel (referee)
Maintaining the chromosome continuity and complete genetic information in human cells is crucial for cell survival and the whole organism. It prevents life-threatening pathologies and preserves genetic continuity. However, cellular DNA is exposed to both endogenous and exogenous stress damaging its content and integrity. This stress activates mechanisms involving detection and repair of these damaged sites (DDR). One of the most serious types of DNA damage double-stranded breaks (DSB) occuring when both strands are severed. DSBs trigger wave of PTMs that regulate protein interactions, nuclear localization and catalytic activity of hundreds of proteins. Such modifications include acetylation, methylation, SUMOylation, ubiquitinylation and especially phosphorylation. The most important kinases involved in DDR kinases are ATM, ATR and DNA-PK. These kinases are activated immediately after the detection of the damaged area. DAXX (Death-associated protein 6) is an adapter and predominantly nuclear protein, which is involved in chromatin remodeling, gene expression modulation, antiviral response and depositing histone H3.3 variants into chromatin or telomeres. Daxx is essential for murine embryogenesis, since the homozygous deletion is lethal in E9.5-10. In 2006 a study mapping the substrates of kinases...
The role of 53BP1 in the cellular response to double-strand DNA breaks
Liďák, Tomáš ; Macůrek, Libor (advisor) ; Rösel, Daniel (referee)
DNA damage may result in various pathological conditions and contributes to aging and development of cancer. Evolutionarily conserved DNA damage response prevents the acumulation of mutations and protects against genomic instability. Tumor suppressor p53-binding protein 1 (53BP1) is an important regulator of the cellular response to DNA double-strand breaks (DSB) and is a canonical component of ionizing radiation-induced foci which are formed at DNA DSB following radiation exposure. Recently, new insights have been gained into its functions in the DNA damage response. Apart from its subtle role in the DNA damage checkpoints signaling, 53BP1 is a well established player in the DNA DSB repair pathway choice. The outcome of DNA repair is influenced by 53BP1 in several contexts. 53BP1 controls 5' end resection at DNA ends, improves DSB repair in heterochromatin, promotes the mobility of uncapped telomeres and mediates synapsis of DNA ends during V(D)J and class switch recombination. 53BP1 contributes to repair defect in BRCA1 (breast cancer type 1 susceptibility protein)-deficient cells, which may have an impact on the treatment of some types of breast cancer. The aim of this bachelor's thesis is to summarize new findings about the role of 53BP1 in the cellular response to DNA DSB. Powered by TCPDF (www.tcpdf.org)
The role of the Smc5/6 complex in DNA viral infection
Protivová, Eliška ; Huerfano Meneses, Sandra (advisor) ; Pokorná, Karolína (referee)
The Smc5/6 complex is an eukaryotic protein complex that, together with Smc1/3 cohesin and Smc2/4 condensin, is involved in ensuring genome stability. It contributes to this by participating in the organization and maintenance of chromosomal structures as well as in the response to DNA damage. In addition, the Smc5/6 complex has been shown to play an important role in viral infection. This thesis focuses on the mechanisms of interaction of the Smc5/6 complex with viral DNA genomes, DNA intermediate genomes and viral proteins. In the case of HBV of the Hepadnaviridae family, Smc5/6 acts as a restriction factor. The same is true for HSV-1 of the Herpesviridae family, viruses of the Papillomaviridae family and HIV-1 of the Retroviridae family. An interaction of the Smc5/6 complex with the JC virus of the Polyomaviridae family has also been discovered. Nevertheless, the meaning of this interaction remains elusive. Some of the above-mentioned viruses can prevent this restriction. In detail, HBx protein of HBV mediates proteasomal degradation of the Smc5/6 complex or Vpr protein of HIV-1 induces degradation of the SLF2 protein, which is responsible for the Smc5/6 localization on HIV-1 DNA intermediate genomes. Keywords: Smc5/6 complex, DNA repair, ATPase, sumoylation, DNA viruses, viruses with a DNA...
Role of yeast WSS1 protease in DNA repair.
Adámek, Michael ; Grantz Šašková, Klára (advisor) ; Čáp, Michal (referee)
Sustaining the integrity of DNA throughout the lifetime is critical for every living organism. Therefore organisms evolved numerous ways to detect and repair different types of DNA damage caused by various endogenous and exogenous factors resulting in replication stress. Defects in these repair mechanisms can lead to severe human diseases such as neurological disorders, familial cancers or developmental syndromes. In presented master thesis, we investigated the function of a yeast protein named Wss1, a metalloprotease that participates in a recently discovered DNA repair pathway that proteolytically removes DNA-protein crosslinks. Wss1 shows strong negative interaction with another DNA repair protease, Ddi1, in which case was discovered, that double-deleted yeast strain lacking WSS1 and DDI1 is hypersensitive to hydroxyurea. Hydroxurea is a ribonucleotide reductase inhibitor that, in the end, arrests cells in the S-phase of cell-cycle. Based on previous studies, we performed rescue experiments with various deletions and single-site mutants of Wss1p to assess the involvement of particular yeast Wss1p domains in the replication stress response to hudroxyurea.
Structure and molecular mechanisms of DNA repair by Nei glycosylase
Landová, Barbora ; Šilhán, Jan (advisor) ; Lux, Vanda (referee)
Abasic sites (Ap site, from apurinic/apyrimidinic) are one of the most common lesions generated in DNA by spontaneous base loss or DNA repair processes. There are two equilibrating forms of an Ap site - ring-open aldehyde and cyclic hemiacetal. Ring- opened aldehydes are reactive electrophilic groups capable of formation covalent adduct with nucleophilic sites in DNA. DNA interstrand cross-link (ICL) resulting from the Ap sites is formed spontaneously as a covalent bond between ring-open aldehyde and amin group of adenin residue in the opposite strand of double stranded DNA. ICLs block DNA replication and transcription. The formation of Ap site derived ICL is relatively long process taking several hours. We assume that the ring-opening of an abasic site is the rate-limiting step in the formation of the thermodynamic ICL. However, formation, stability and DNA repair of Ap-ICL are still poorly understood processes. Here, I have set up mechanistic in vitro experiments to reveal and calculate the probability of Ap-ICl formation in vivo. In more detail, I study the rates of formation of Ap-ICLs in the sequence context of neighbouring nucleotides of freshly formed covalent bond of ICL. I focus on sequence preference, the influence of AT/ GC rich regions and the length of oligonucleotides. I have...
The Role of DNA Repair in the Onset and Therapy of Ovarian Cancer
Tomášová, Kristýna ; Vodička, Pavel (advisor) ; Čáp, Michal (referee)
DNA repair and DNA damage response are very important biological systems, inevitable to maintain genomic stability and fidelity of the genetic information, for the onset of ovarian cancer. Further, DNA repair is also substantially involved in the response to the therapy, since many chemotherapeutics act as DNA damaging agents. This literary analysis is intended to survay the relevance of DNA repair to ovarian carcinogenesis. Special emphasis is placed on repair defects, as it is inextricably associated with the onset of cancer and treatment outcome. Apart from well-known alternations in ovarian cancer susceptibility genes, such as BRCA1 and BRCA2 involved in homologous recombination repair, ample space will be dedicated to less common gene mutations across different repair pathways. Research confirms that abnormalities in the proteins responsible for homologous recombination repair are the leading cause of ovarian cancer. The majority of authors also suggested that targeting DNA repair pathways, especially base excision repair, can improve chemotherapy efficiency in a synergic manner. The same applies to nucleotide excision repair, which repairs platinum-DNA adducts and thus contibutes to platinum drugs resistance emerging. By way of contrast, mismatch repair in ovarian cancer is rather poorly...
Posttranslational modification of the adapter protein DAXX in the cellular response to genotoxic stress
Bražina, Jan ; Anděra, Ladislav (advisor) ; Černý, Jan (referee) ; Vodička, Pavel (referee)
Maintaining the chromosome continuity and complete genetic information in human cells is crucial for cell survival and the whole organism. It prevents life-threatening pathologies and preserves genetic continuity. However, cellular DNA is exposed to both endogenous and exogenous stress damaging its content and integrity. This stress activates mechanisms involving detection and repair of these damaged sites (DDR). One of the most serious types of DNA damage double-stranded breaks (DSB) occuring when both strands are severed. DSBs trigger wave of PTMs that regulate protein interactions, nuclear localization and catalytic activity of hundreds of proteins. Such modifications include acetylation, methylation, SUMOylation, ubiquitinylation and especially phosphorylation. The most important kinases involved in DDR kinases are ATM, ATR and DNA-PK. These kinases are activated immediately after the detection of the damaged area. DAXX (Death-associated protein 6) is an adapter and predominantly nuclear protein, which is involved in chromatin remodeling, gene expression modulation, antiviral response and depositing histone H3.3 variants into chromatin or telomeres. Daxx is essential for murine embryogenesis, since the homozygous deletion is lethal in E9.5-10. In 2006 a study mapping the substrates of kinases...

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