Дисертації з теми "RecQ4 helicases"
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THANGAVEL, SARAVANA BHAVAN. "Characterization of the Role of RecQ helicases in human DNA replication." Doctoral thesis, Scuola Normale Superiore, 2010. http://hdl.handle.net/11384/85963.
Повний текст джерелаMojumdar, Aditya. "Structural and Biochemical study of human RECQ4." Doctoral thesis, Università degli studi di Trieste, 2015. http://hdl.handle.net/10077/11141.
Повний текст джерелаRecQ helicases belong to a ubiquitous family of DNA unwinding enzymes that are essential to maintain genome stability by acting at the interface between DNA replication, recombination and repair. Humans have five different paralogues of RecQ helicases namely RecQ1, BLM, WRN, RecQ4 and RecQ5. This work focuses on the structural and biochemical study of human RecQ4. Germ-line mutations in the RECQ4 gene give rise to three distinct human genetic disorders (Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes). Despite the important roles of RecQ4 in various cellular processes, RecQ4 have never been fully characterized. In addition to the helicase domain, RecQ4 has a unique N-terminal part that is essential for viability and is constituted by a region homologous to the yeast Sld2 replication initiation factor, followed by a cysteine-rich region, predicted to fold as a Zn knuckle. A part of this work focuses on the structural and biochemical analysis of both the human and Xenopus RecQ4 cysteine-rich regions, and shows by NMR spectroscopy that the Xenopus fragment does indeed assumes the canonical Zn knuckle fold, whereas the human sequence remains unstructured, consistent with the mutation of one of the Zn ligands. Both the human and Xenopus Zn knuckles bind to a variety of nucleic acid substrates, with a preference for RNA. We also investigated the effect of an additional Sld2 homologous region upstream the Zn knuckle. In both the human and Xenopus system, the presence of this region strongly enhances binding to nucleic acids. These results reveal novel possible roles of RecQ4 in DNA replication and genome stability. Recently the catalytic core of RecQ4 has been predicted to include RecQ-like-C-terminal (RQC) domain at the C-terminus of the helicase domain, similar to other RecQ helicases. This domain is composed of a Zn-binding region and a winged helix (WH) domain. Another part of this thesis centers on the structural and biochemical characterization of the catalytic core of RecQ4 including the helicase and RQC domain. The results provide an insight in the Zn binding ligands present in the RQC domain that plays a role in DNA binding and unwinding activity of the protein. Also the presence of the characteristic aromatic residue at the tip of the WH β hairpin and its role in DNA binding and unwinding has been established. Finally, it provides a low resolution SAXS model of the catalytic core of RecQ4.
Elicasi RecQ appartengono a una famiglia ubiquitaria di DNA svolgimento enzimi che sono essenziali per mantenere la stabilità del genoma agendo all'interfaccia tra replicazione del DNA, ricombinazione e riparazione. Gli esseri umani hanno cinque diversi paralogues di RecQ elicasi cioè RecQ1, BLM, WRN, RecQ4 e RecQ5. Questo lavoro si concentra sullo studio strutturale e biochimica di RecQ4 umana. Mutazioni germinali nel gene RECQ4 danno luogo a tre malattie genetiche umane distinte (Rothmund-Thomson, RAPADILINO e sindromi Baller-Gerold). Nonostante i ruoli importanti di RecQ4 in diversi processi cellulari, RecQ4 non sono mai stati pienamente caratterizzato. In aggiunta al dominio elicasi, RecQ4 ha una parte unica N-terminale che è essenziale per la vitalità ed è costituito da una regione omologa al lievito Sld2 fattore di iniziazione replica, seguita da una regione ricca di cisteina, previsto per piegare come stinco Zn . Una parte di questo lavoro si concentra sull'analisi strutturale e biochimica sia della regioni ricche di cisteina Xenopus RecQ4 umana e, e spettacoli di spettroscopia NMR che il frammento Xenopus effettivamente assume la canonica Zn nocca volte, mentre la sequenza di resti umani non strutturato, coerente con la mutazione di uno dei ligandi Zn. Sia il nocche Xenopus Zn umana e si legano ad una varietà di substrati di acido nucleico, con una preferenza per l'RNA. Abbiamo anche studiato l'effetto di un ulteriore regione omologa Sld2 monte la nocca Zn. Sia il sistema Xenopus umano e, la presenza di questa regione migliora fortemente legame ad acidi nucleici. Questi risultati rivelano possibili ruoli nuovi di RecQ4 nella replicazione del DNA e la stabilità del genoma. Recentemente il nucleo catalitico di RecQ4 stato previsto per includere RecQ-like-C-terminale (RQC) dominio al C-terminale del dominio elicasi, simile ad altri elicasi RecQ. Questo dominio è costituito da una regione-Zn vincolanti e un'elica alato (WH) dominio. Un'altra parte di questa tesi incentrata sulla caratterizzazione strutturale e biochimica del nucleo catalitico della RecQ4 compreso il elicasi e il dominio RQC. I risultati forniscono una descrizione nel Zn ligandi presenti nel dominio RQC che svolge un ruolo nel legame al DNA e l'attività svolgimento della proteina legante. Inoltre è stata stabilita la presenza della caratteristica residuo aromatico sulla punta della forcella WH β e il suo ruolo nel legame al DNA e di svolgimento. Infine, esso fornisce una bassa risoluzione SAXS modello del nucleo catalitico di RecQ4.
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Ren, Hua. "Aspects moléculaires des hélicases de la famille de RecQ." Phd thesis, École normale supérieure de Cachan - ENS Cachan, 2009. http://tel.archives-ouvertes.fr/tel-00448084.
Повний текст джерелаKaiser, Sebastian [Verfasser], and Caroline [Gutachter] Kisker. "A RecQ helicase in disguise: Characterization of the unconventional Structure and Function of the human Genome Caretaker RecQ4 / Sebastian Kaiser ; Gutachter: Caroline Kisker." Würzburg : Universität Würzburg, 2019. http://d-nb.info/1206879246/34.
Повний текст джерелаGuo, Rongbing. "Biochemical and structural characterization of BLM Helicase." Paris 11, 2008. http://www.theses.fr/2008PA112168.
Повний текст джерелаBloom's syndrome (BS) is an autosomal recessive disorder, showing high frequency of sister chromatid exchange in lymphocyte of the patients. Since BS is preposition of a wide spectrum of cancer, the syndrome has been studied for understanding of the mechanism of cancer extensively. Ln the first part, we proved the existence of a zinc-binding domain in which a zinc ion is coordinated by four cysteines residues in RecQ-Ct domain of BLM. This conclusion is drawn from our biophysical and biochemical studies. We modeled the 3D structure of BLM protein based on that of E. Coli RecQ helicase, which revealed a similar structural domain in both helicases that coordinate zinc. The results from experiments with three mutants showed that their enzymatic activities were severely reduced or abrogated. The demetalization of zinc from BLM had no influence on the activities of BLM, but it would decrease the themostability of the protein. Ln conclusion, BLM contains a zinc binding domain with one zinc ion in each protein. The second part of our studies includes the work for understanding of causative molecular mechanism of missense mutations which happened in helicase domain of BLM found in BS patients. On the basis of the work inthe fist part, we further modeled the 3D structure of BLM in complex with A TPyS and DNA. With the model, we deduced the possible causative mechanism of mutants. We produced mutant proteins and purified them to homogeneity. The A TPase activity, A TP binding activity, DNA binding activity and helicase activity ofthe mutants were ail checked. Ln conclusion 1 showed that: 1. BLM642-129o possibly employ an "inchworm" model mechanism; 2. Amino acid residues from 861 to 901 are imprtant for DNA binding; 3. DNA binding ofBLM is mainly controlled by lobe2 and lobe3, lobel contribute to a transient ssDNA binding; 4. The annealing activity of RecQ helicase suggests a weak DNA binding activity
Budhathoki, Jagat B. "Interactions of RecQ-Family Helicases with G-quadruplex Structures at the Single Molecule Level." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1467765011.
Повний текст джерелаHuber, Michael D. "Structure-function analysis and substrate specific inhibition of RecQ helicases /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/9253.
Повний текст джерелаBajpai, Sailesh. "Analysis of human RECQ1 helicase function in cells." Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522223.
Повний текст джерелаLevitt, Nicola C. "Role of RecQ helicases in maintenance of genome integrity." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275469.
Повний текст джерелаLucic, Bojana. "Understanding the structural basis of the human RECQ1 helicase function." Thesis, Open University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536078.
Повний текст джерелаPopuri, Venkateswarlu. "Structural and biochemical characterization of the human recq 1 helicase." Thesis, Open University, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.489896.
Повний текст джерелаMirzaei-Souderjani, Hamed. "Functional and mutational analysis of human RecQ-Like DNA helicases in Saccharomyces cerevisiae." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4547.
Повний текст джерелаNovoa, Carolina. "RecQ-like helicase SGS1 counteracts DNA : RNA hybrid induced genome instability." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/60964.
Повний текст джерелаScience, Faculty of
Graduate
Harrison, Ryan M. "Molecular biophysics of strong DNA bending and the RecQ DNA helicase." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:f02fc167-b705-4275-a413-21d13b5d94c3.
Повний текст джерелаSyed, Salahuddin. "Nonreplicative DNA Helicases Involved in Maintaining Genome Stability." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6408.
Повний текст джерелаChaix, Alexandre. "Genetic analysis and meiotic role of the Saccharomyces cerevisiae RecQ helicase SGS1." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/30371.
Повний текст джерелаSilva, João Paulo Lopes da. "Comparação dos Perfis Transcricionais de Genes de Reparo e Duplicação do DNA e Medidas de Comprimento Telomérico entre Grupos de Indivíduos Jovens, Idosos e Centenários." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-28072015-114601/.
Повний текст джерелаGenomic instability plays a major role in the aging process due to the accumulation of DNA damage in somatic cells continuously exposed to endogenous and exogenous factors. A group of proteins essential in maintaining genome stability is composed by RecQ helicase, acting in several cell metabolism processes such as DNA replication, recombination, DNA repair and telomere maintenance. Some evidence related the aberrant expression of these proteins to premature aging. In order to determine the transcriptional expression profile of RecQ helicase gene family and some genes involved in the BER (Base excision repair) pathway, such as PARP1, POL and APEX1 in peripheral blood mononuclear cells (PBMCs), we compared groups of young (n = 20), elderly (n = 17) and centenarians (n = 27). Furthermore, it was also evaluated telomere length in DNA samples from these individuals. It was observed a decrease in the transcriptional expression of BLM gene in elderly and centenarians compared to the young group (p <0.05). It was also observed a decrease in expression of RECQL5 gene in the elderly compared to the younger group. For the BER genes, it was observed a transcriptional repression of PARP1 in the elderly group compared to the young group (p <0.05). Regarding the telomere length, our results demonstrated an association between reduction of telomere length and age. We obtained significant difference in comparing the telomere length of the elderly and centenarians compared to the younger group. However, no difference was observed between the elderly and centenarians groups. Thus, our results show an association of aging process with the modulation of certain genes from RecQ helicase family and participants of the BER pathway and the telomere shortening. The results generated in this study are promising, and relevant to better understanding the aging process.
Viziteu, Elena. "RECQ1 Helicase Involvement in the Resistance to Replication Stress and Chemotherapy in Multiple Myeloma Myélome Multiple." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTT008.
Повний текст джерелаMultiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the clonal expansion of multiple myeloma cells (MMCs), primarily in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the genes downregulated by DNMT inhibitor. RECQ helicase are DNA unwinding enzymes involved in the maintenance of chromosome stability. RECQ1 silencing in cancer cells results in mitotic catastrophe and prevents tumor growth in murine models. RECQ1 is significantly overexpressed in primary myeloma cells compared to normal plasma cells and in myeloma cell lines compared to primary myeloma cells of patients. High RECQ1 expression is associated with a poor prognosis in two independent cohorts of patients. RECQ1 knock down inhibits growth of myeloma cells and induces apoptosis. Given the known role of RECQ1 in replication and DNA repair activation, the effect of RECQ1 depletion in DNA damage response was investigated. RECQ1 depletion induced spontaneous accumulation of DNA double strand breaks (DSBs) evidenced by the phosphorylation of ATM and H2AX histone and detection of 53BP1 foci. Using an alkaline comet assay, a significant increase in DNA strand breaks was confirmed in RECQ1 depleted cell lines compared to control. RECQ1 depletion was associated with CHK1 and CHK2 phosphorylation in MM cells. Since RECQ1 depletion is associated with DNA damage response activation and DNA strand breaks formation, a link between RECQ1 expression and drug sensitivity was hypothesized. RECQ1 overexpression significantly protects myeloma cell lines from melphalan and bortezomib-induced apoptosis. Furthermore, RECQ1 depletion sensitizes myeloma cells to treatment. Using immunoprecipitation, RECQ1 was shown to interact with PARP1 but not RAD51 or MSH2. An increased association of the two proteins was found upon DNA damages induced by melphalan. In agreement, RECQ1 depletion sensitizes myeloma cell lines to PARP inhibitor. We identified RECQ1 as a miR-203 target. Interestingly, aberrant methylation of miR-203 was reported in MM cells and treatment with 5-aza-2’-deoxycitidine led to promoter demethylation and miR-203 re-expression. Furthermore, anti-miR-203 treatment induced a significant increase of RECQ1 mRNA level in MM cells.In conclusion, RECQ1 represent a biomarker of drug resistance in MM, which is targeted by DNMT inhibitors. This suggests association of alkylating agents and/or PARP inhibitors with DNMT inhibitor may represent a therapeutic approach in RECQ1high patients associated with a poor prognosis
Klaue, Daniel. "DNA Unwinding by Helicases Investigated on the Single Molecule Level." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-97596.
Повний текст джерелаJeder Organismus ist bestrebt, die genetischen Informationen intakt zu halten, die in seiner DNA gespeichert sind. Dies wird durch präzise gesteuerte zelluläre Prozesse wie DNA-Replikation, -Reparatur und -Rekombination verwirklicht. Ein wesentlicher Schritt ist dabei das Entwinden von DNA-Doppelsträngen zu Einzelsträngen. Diese chemische Reaktion wird von Helikasen durch die Hydrolyse von Nukleosidtriphosphaten katalysiert. Obwohl bei allen Helikasen bestimmte Aminosäuresequenzen hoch konserviert sind, können sie sich in Eigenschaften wie Struktur, Funktion oder DNA Substratspezifität stark unterscheiden. Gegenstand der vorliegenden Arbeit ist es, die Entwindungsmechanismen von drei verschieden Helikasen aus zwei unterschiedlichen Organismen zu untersuchen, die sich in ihrer Struktur sowie ihrer Funktion unterscheiden. Es handelt sich dabei um die replikative, hexamerische Helikase Large Tumor-Antigen (T-Antigen) vom Simian-Virus 40 und die DNA-Reparatur-Helikasen RecQ2 und RecQ3 der Pflanze Arabidopsis thaliana. Um DNA-Entwindung in Echtzeit zu untersuchen, wird eine biophysikalische Einzelmolekültechnik, die \"Magnetische Pinzette\", verwendet. Mit dieser Technik kann man ein DNA-Molekül, das an ein magnetisches Partikel gebunden ist, strecken und gleichzeitig dessen Gesamtlänge messen. Mit speziellen DNA-Konstrukten kann man so bestimmte Eigenschaften der Helikasen bei der DNA-Entwindung, wie z.B. Geschwindigkeit, Länge der entwundenen DNA (Prozessivität) oder den Einfluß von Kraft, ermitteln. Es wird gezeigt, dass T-Antigen eine der langsamsten und prozessivsten Helikasen ist. Im Gegensatz zu prokaryotischen Helikasen ist die Entwindungsgeschwindigkeit von T-Antigen kaum kraftabhängig. Aktuelle Modelle sagen dieses Verhalten nicht vorraus, weshalb ein alternatives Modell entwickelt wird. Die untersuchten RecQ-Helikasen zeigen ein Entwindungsverhalten bei dem permanent kurze Abschnitte von DNA entwunden und wieder zusammengeführt werden. Dieses Verhalten wird hier zum ersten Mal unter dem Einfluß externer Kräfte gemessen. Es wird gezeigt, dass die permanente Entwindung auf die Fähigkeit beider Helikasen, von einem einzelen DNA-Strang auf den anderen zu wechseln, zurückzuführen ist. Obwohl RecQ2 und RecQ3 beide das Verhalten des permanenten Entwindens aufzeigen, unterscheiden sie sich stark in anderen Eigenschaften. Der gravierendste Unterschied ist, dass RecQ2 wie eine klassische Helikase die DNA entwindet, während RecQ3 eher bestrebt ist, die DNA-Einzelstränge wieder zusammenzuführen. Die unterschiedlichen Eigenschaften könnten die verschieden Aufgaben beider Helikasen während DNA-Reparaturprozessen widerspiegeln. Weiterhin werden die experimentellen Methoden optimiert, um möglichst hohe Auflösungen der Daten zu erreichen. Dazu zählen der Aufbau einer verbesserten und stabileren \"Magnetischen Pinzette\" mit sub-nanometer Auflösung und die Entwicklung neuer Methoden, um DNA Konstrukte herzustellen. Außerdem wird die Torsions\\-steifigkeit von magnetischen Partikeln in externen magnetischen Feldern untersucht. Dabei finden sich Auswahlkriterien für DNA-gebundene magnetische Partikel, durch die eine hohe Auflösung erreicht wird
Liew, Li Phing. "Characterization of the TLH1-4+ telomere-linked recq DNA helicase genes in schizosaccharomyces pombe." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510984.
Повний текст джерелаMarple, Teresa C. "Brca2 and Blm have opposing functions in response to DNA damaging agents and in the maintenance of mouse major satellite repeat DNA : a dissertation /." San Antonio : UTHSC, 2006. http://proquest.umi.com/pqdweb?did=1216730631&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
Повний текст джерелаLangland, Gregory Todd. "Interaction Between the BLM Helicase and the DNA Mismatch Repair Protein, MLH1." University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1052316756.
Повний текст джерелаZheng, Lu. "The role of human RECQ5 helicase in the maintenance of genomic stability revealed by protein-protein interaction study /." [S.l.] : [s.n.], 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000281175.
Повний текст джерелаCampos-Doerfler, Lillian. "The Role of Sgs1 and Exo1 in the Maintenance of Genome Stability." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/7006.
Повний текст джерелаVeith, Sebastian [Verfasser]. "Studies on the regulation of genome maintenance factors by non-covalent interaction with poly(ADP-ribose) with a focus on RECQL helicases / Sebastian Veith." Konstanz : Bibliothek der Universität Konstanz, 2016. http://d-nb.info/1154684679/34.
Повний текст джерелаSangrithi, Mahesh Nataraj. "Insights into the functions of a novel vertebrate RecQ helicase in chromosomal DNA replication and in the response to stalled replication forks." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616261.
Повний текст джерелаWillis, Nicholas Adrian. "Checkpoint Regulation of Replication Forks in Response to DNA Damage: A Dissertation." eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/427.
Повний текст джерелаLees, Hayley Diane. "Molecular mechanisms of premature ageing in a worm model of human Werner syndrome." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:080df619-828b-4248-b03f-c4aeb31f1672.
Повний текст джерелаDutertre, Stéphanie. "Analyse de l'expression et des modifications post-traductionnelles de l'hélicase BLM au cours du cycle cellulaire." Paris 11, 2001. http://www.theses.fr/2001PA11T022.
Повний текст джерелаBloom's syndrome is a rare genetic disorder associated to a predisposition to the development of all kinds of cancer and to a generalized genetic instability BLM protein is defective in this disorder and belongs to the recQ helicase family. Helicases of this family are extremely conserved throughout evolution and are involved in the control of recombination. The BLM protein displays a 3'-5' DNA helicase activity; however its physiological role is still unclear. The goal of my research work was the elucidation of that role. We showed that BLM protein accumulates in S phase; of the cell cycle that its expression persists during G2/M and sharply declines in G1. We also showed that BLM helicase is subject to post-translational modifications during mitosis, namely phosphorylations modifying its cellular localization. We showed that BLM phosphorylation in mitosis-arrested cells does not modify neither its helicase activity nor its interaction with topoisomerase IIIα. Besides, we showed that, in response to ionizing radiation, BLM protein accumulates and is phosphorylated through an ATM-dependent pathway. We also showed that ionizing radiation treatment of mitosis arrested cells, results in BLM dephosphorylation and in inactivation of the Cdc2 kinase. This dephosphorylation is associated to a change in BLM localization towards an insoluble cellular compartment. These results suggest that BLM protein is involved in the cellular response to ionizing radiation and that it can be stored during mitosis under an active form in a soluble compartment of the mitotic cells allowing its recruitment in response to DNA damage. All these results suggest the existence of a general mechanism of DNA repair during mitosis in response to genotoxic stress
Li, Kai. "Regulation of WRN Function by Acetylation and SIRT1-Mediated Deacetylation in Response to DNA Damage: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/511.
Повний текст джерелаΝαθαναηλίδου, Πατρούλα. "Μελέτη του ορθολόγου της ελικάσης RecQ4, Hrq1, στον σχιζοσακχαρομύκητα". Thesis, 2014. http://hdl.handle.net/10889/8394.
Повний текст джерелаThe maintenance of genome integrity is essential for cell survival and therefore for survival of the organism. There are two major factors contributing to the preservation of genome stability: acurate DNA replication, which is important for the intact transfer of the genome to the next generation and DNA repair mechanisms, which act in the presence of DNA damage.There are many different molecules involved in the aforementioned cellular processes, including a helicase called, RecQ4. This enzyme belongs to the evolutionarily conserved family of RecQ helicases and is one of the five members of the family, in humans. RecQ4 is linked to Rothmund-Thomson premature aging syndrome and it is unique amongst RecQ helicases in being required for the normal initiation of DNA replication. Studying RecQ4 in humans has difficulties, because of the complexity of the system. In fission yeast, the RecQ4 homologue, called Hrq1, has been recently recognized as a member of the family and there is limited evidence, concerning its function. The study of Hrq1 in a model system, like fission yeast, will not only elucidate its role in this organism, but will also assist in understanding the role of its human orthologue. In the first part of this study we determined the role of Hrq1 helicase in DNA replication, by observing phenotypic changes in cells bearing the helicase deletion, compared to wild-type cells. We, also, investigated protein-protein interactions between Hrq1 and molecules related to the process of DNA replication in Schizosaccharomyces pombe, using co-immunoprecipitation. In the second part, the role of Hrq1 in DNA damage repair was investigated. Specifically, we examined how Hrq1 affects the cellular response to cisplatin, using phenotypic analysis. Finally, we looked into protein-protein interactions of Hrq1, that are related to the regulation of its expression in vivo.
Kaiser, Sebastian. "A RecQ helicase in disguise: Characterization of the unconventional Structure and Function of the human Genome Caretaker RecQ4." Doctoral thesis, 2020. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-160414.
Повний текст джерелаVom simpelsten einzelligen Organismus bis hin zu hoch komplexen Lebensformen, genetische Information in Form von DNA repräsentiert die universelle Grundlage aller biologischer Prozesse, und damit die des Lebens selbst. Die Aufrechterhaltung der intakten Struktur und Funktion des Genoms ist daher von höchster Priorität für jede einzelne Zelle. Die DNA selbst, als aktives und komplexes Makromolekül, ist sowohl Substrat als auch Produkt einer Vielzahl dieser biochemischen Prozesse. Ein wesentlicher Aspekt für die Aufrechterhaltung genomischer Integrität besteht daher in der gezielten Regulation aller Prozesse des DNA Metabolismus, um die Konservierung der DNA in Sequenz und Funktion zu gewährleisten und unerwünschte Nebenreaktionen zu verhindern. Die Familie der RecQ Helikasen hat sich als eine essentielle Gruppe von Enzymen etabliert, die diese genomische Integrität gewährleisten, indem sie eine Vielzahl von DNA basierten Prozessen kontrollieren. Dies umfasst die Replikation, Reparatur, Rekombination und Transkription von DNA, sowie Prozesse, die der Stabilisierung der Telomere dienen. RecQ Helikasen werden von allen Zellen exprimiert und können in allen Domänen des Lebens – Bakterien, Archaeen und Eukaryoten nachgewiesen werden. Humane Zellen enthalten fünf verschiedene RecQ Helikasen, RecQ1, BLM, WRN, RecQ4 und RecQ5, welche sowohl individuelle als auch überlappende Funktionen in der Aufrechterhaltung genomischer Integrität innehaben. Eine Beeinträchtigung der Funktion der humanen RecQ Helikasen BLM, WRN und RecQ4 führt zu Krankheiten die durch eine erhöhte Wahrscheinlichkeit für die Entstehung von Krebs gekennzeichnet sind. Dies unterstützt die Theorie, dass die genomische Instabilität eine molekulare Grundlage für die Entstehung von Krebs darstellt. Allerdings repräsentiert die den RecQ Helikasen innewohnende Funktion der Aufrechterhaltung genomischer Integrität ein zweischneidiges Schwert. Während ihre Aktivitäten auf der einen Seite für normale Zellen essentiell sind, um Krankheiten und zelluläre Alterungserscheinungen zu verhindern, wird ihre DNA protektive Funktion von Krebszellen genutzt, indem sie verschiedenste RecQ Helikasen überexprimieren und damit den nachteiligen Effekten der unkontrollierten DNA Replikation entgegenwirken. Zudem erlangen Tumorzellen durch die erhöhte Präsenz der RecQ Helikasen Resistenz gegenüber einer Vielzahl von Chemotherapeutika. Es ist daher von größter Bedeutung zu verstehen, wie genau die einzelnen RecQ Helikasen in der Entstehung von Krebs und dem Alterungsprozess involviert sind, um neue Ansätze in der Krebstherapie zu entwickeln. Die vorliegende Arbeit präsentiert und diskutiert die erste detaillierte Röntgen-Kristallographische Struktur der humanen RecQ4 Helikase. Die vorgestellte Struktur umfasst den konservierten Kern der RecQ4 Helikase, einschließlich eines großen Teils ihres einzigartigen C-terminus. Eine Analyse des RecQ4 Modells weist sowohl eindeutige Unterschiede als auch unerwartete Gemeinsamkeiten im Vergleich mit anderen, untereinander strukturell und funktional ähnlichen, humanen RecQ Helikasen auf und erlaubt zudem Rückschlüsse auf die Funktion der einzigartigen C-terminalen RecQ4 Domäne. Die biochemische Charakterisierung verschiedener RecQ4 Varianten liefert funktionelle Einblicke in den Mechanismus der DNA Doppelstrangtrennung durch RecQ4 und deutet darauf hin, dass sich dieser in weiten Teilen vom Mechanismus der anderen humanen RecQ Helikasen unterscheidet. Letztlich repräsentiert das hier vorgestellte Modell der RecQ4 Helikase die Grundlage für die Analyse verschiedenster dokumentierter RecQ4 Patientenmutationen und erlaubt damit eine erste Abschätzung von Struktur-und-Funktions-Beziehungen bezüglich der bekannten RecQ4- assoziierten Krankheitsbilder
Capp, Christopher Lee. "The Biochemical Characterization of Drosophila melanogaster RecQ4 Helicase." Diss., 2011. http://hdl.handle.net/10161/3814.
Повний текст джерелаRecQ4, a member of the conserved RecQ family of helicases, is involved in replication and associated with several clinical syndromes. Although biologically important, the biochemistry of RecQ4 has remained elusive. We have expressed and purified Drosophila melanogaster RecQ4 from a baculovirus expression system. Biochemical characterization of the helicase, ATP hydrolysis, annealing, and binding activities of the enzyme has been performed, using native and non-native gel electrophoresis and thin layer chromatography, among other techniques. These reveal that RecQ4 is a 3' to 5' helicase that is stimulated by the presence of single-stranded DNA 3' of the duplex DNA region to be unwound. The enzyme is also capable of annealing complementary DNA strands, though this is inhibited by AMPPNP, a non-hydrolyzable analog of ATP. RecQ4 also forms a stable complex with single-stranded DNA in the presence of AMPPNP. We argue that the helicase activity of RecQ4 is important to the process of DNA replication. This leads to the conclusion that two helicases, RecQ4 and the Mcm2-7 complex, are involved in replication. The manner of their simultaneous involvement is not intuitive, and so models by which the two enzymes may cooperate are discussed.
Dissertation
Shereda, Robert D. "Biochemical complexes of RecQ deoxyribonucleic acid helicases." 2008. http://www.library.wisc.edu/databases/connect/dissertations.html.
Повний текст джерелаKilloran, Michael Paul. "Specialization of multiple HRDC domains in bacterial RecQ helicases." 2008. http://www.library.wisc.edu/databases/connect/dissertations.html.
Повний текст джерелаZittel, Morgan C. "Molecular mechanisms underlying the deoxyribonucleic acid helicase activity of Escherichia coli recQ." 2007. http://www.library.wisc.edu/databases/connect/dissertations.html.
Повний текст джерелаLu, Chia-Yin, and 盧佳吟. "Characterization of the roles of post-translational modifications of RecQ helicase, Sgs1p, in Saccharomyces cereveciae." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/99530661793694536368.
Повний текст джерела國立臺灣大學
微生物學研究所
97
Mutations in genes encoding WRN and BLM RecQ DNA helicases lead to genome instability, premature aging and cancer predisposition syndromes. The Saccharomyces cerevisiae Sgs1 RecQ helicase safeguards genome integrity through its function in DNA recombination. RecQ homologues, WRN and BLM were all previously shown to be undergoing several post-translational modifications (PTMs), such as sumoylation, phosphorylation and acetylation. In this report, we identify the conditions under which Sgs1 sumoylation is induced, and clarify the role of this modification in different types of recombinational repair. We found that the Lysine 621 residue is critical for sumoylation in vivo and in vitro. We demonstrate that Sgs1 is specifically sumoylated under the stress of double strand breaks (DSBs). Sumoylation of Sgs1 promotes telomere-telomere recombination. In contrast, sumoylation of Sgs1 is dispensable for other functions of Sgs1, including damage recovery, homologous recombination, regulation of top3 slow growth and rDNA recombination. Our observations indicate that sumoylation on Sgs1 modulates the outcome in telomere recombination. Moreover, we also observed that Sgs1 is phosphorylated in a Cdk1- and cell cycle-dependent manner. We showed that Sgs1 is hyperphosphorylated during S phase and is usually under-phosphorylated in G1 stage. The Cdk1-crippling backgrounds led to diminishment of Sgs1 hyperphosphorylation during S phase. By in vitro kinase assay, I also demonstrated that Sgs1 is directly phosphorylated by Cdk1 in vitro. Here I provided solid evidence that Sgs1 is sumoylated and phosphorylated, and will apply my data to further understood the detail mechanism how these modifications regulate Sgs1 functions.
Fryzelková, Jana. "Úloha helikázy RECQ5 při stabilizaci a opravě replikačních vidlic po jejich kolizi s transkripčním komplexem." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-355971.
Повний текст джерела