Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 29 for “"Replisome"”.
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Elucidation and characterisation of checkpoint kinase interactions with the replisome
… stresses, partly by being recruited to the replisome, the machinery that conducts DNA replication. Regulation of replisome stability is one of the essential functions of these checkpoint kinases. Since replication stress is a cellular feature of many tumours and is a major driver of …
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Large replisome-dependent heterochromatic domains defining the transgenerational regulatory landscape
… been explored in animals. In my thesis, I use replisome-mutant strains of the nematode Caenorhabditis elegans as a model to explore the role of replisome-histone interactions in TEI. These strains show epigenetic-related phenotypes such as deficient inheritance of RNA interference (RNAi) gene …
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In vitro reconstitution of the ubiquitylation and disassembly of the eukaryotic replisome
Maintenance of genomic integrity is dependent on the duplication of chromosomes, only once per cell cycle. Highly conserved mechanisms for the regulation of chromosome replication exists to ensure that the genome is copied only once. The Cdc45-MCM-GINS (CMG) DNA helicase which is the core of the …
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DDI1/2 and RTF2-Dependent Regulation of RNASE H2 at the Replisome Ensures Genome Stability
… Replication Termination Factor 2 (RTF2) from the replisome. Persistence of RTF2 at the replisome compromises the replication stress response, resulting in accumulation of single-stranded DNA, inefficient replication fork restart, genome instability, and cell death. During unperturbed replication, …
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Uncovering vital molecular contacts within the replisome and characterizing fail-safe mechanisms ensuring genomic stability in E. coli.
To study replisome coupling interactions and gain a better understanding of enzymatic communication, we modeled interfacial residues between α-Pol III and τ-CLC. A critical C-terminal linker in the τ-subunit tethers α-Pol III to the DnaB helicase for efficient DNA replication in E. coli. Therefore, …
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Keeping It Together and Taking It Apart: Structural Investigations of Replisome Complexes Involved in DNA Replication Fork Protection and Termination
… responsible for DNA replication is known as the replisome. However, during unwinding and DNA synthesis, the replisome may encounter various obstacles such as DNA damage and tightly-bound proteins, necessitating specific pathways tailored to tolerating and overcoming such hinderances. Upon …
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Functional and structural investigations of human replisomes assembled from purified proteins
… and efficient replication is known as the replisome. At the heart of the eukaryotic replisome is the CMG (CDC45-MCM-GINS) helicase that unwinds the parental DNA duplex to generate single-stranded DNA for initiation of DNA synthesis by Pol α -primase and the replication of both strands by …
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Clamp loading on the leading strand during DNA replication and initial reconstitution of sister chromatid cohesion establishment
… In eukaryotes this process is performed by the replisome, a complex protein machinery composed of a core helicase, DNA polymerases, and a wide range of replisome-associated factors. One such factor is the sliding clamp PCNA, which acts as both a processivity factor to support fast and efficient …
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Functions of RTF2 in DNA Replication and Checkpoint Control
… protein machinery that copies DNA, called the replisome, is dynamically regulated across S phase to promote the accurate and complete duplication of the genome before cell division. Work in our laboratory has uncovered one such dynamic process at replication forks experiencing replication …
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Regulation of DNA replication by PP2A family phosphatases
… Sld2 and Sld3, is sufficient for CDK’s role in replisome activation in Saccharomyces cerevisiae. This modification permits a cascade of protein recruitment to origins that completes replisome assembly, however, Sld2 and Sld3 do not travel with the replisome during replication elongation. It is …
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Understanding the activation mechanism of the Chk1 kinase
… PI3K-like ATR kinase and its recruitment to the replisome via a direct interaction with the core replisome component, Claspin. The Chk1-binding domain of Claspin contains a tandem repeat of three phosphothreonine/serine motifs, which need to be phosphorylated for interaction. However, the …
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Treslin and its role in the assembly of the replicative DNA helicase
… out by a multi-subunit protein complex called replisome. The core of replisome is made up of six-subunit protein ring Mcm2–7, which contains weak DNA helicase activity. In order to fully activate the helicase activity, protein co-activators of Cdc45 and GINS have to be recruited to assemble a …
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Studies of DNA repair and mutagenesis in Escherichia coli and Bacillus subtilis
… via interactions between MMR proteins and the replisome.
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THE IMPACT OF REPLICATION STRESS ON THE EPIGENOME OF MOUSE EMBRYONIC STEM CELLS
… by increased interactions between PRC2, replisome factors, and double-strand breaks. In summary, our findings propose a role for PRC2 in mediating the replication stress response by altering chromatin dynamics, which ultimately expands cell fate by lowering reprogramming barriers. These …
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DNA polymerase interactions and their role In translesion synthesis substitutions.
… is foundational for studies of the human replisome, I then optimized expression and purification protocols to yield human PCNA, RFC, Pol delta, and Pol eta to allow in vitro experimentation of the more complex human system. Through interrogation of a direct interaction between human HiFi …
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Identification of MMS22 as a regulator of DNA repair
… hypersensitive to DNA alkylation that blocks replisome progression. I set out to investigate the cellular roles of these genes and found that cells lacking MMS1 or MMS22 are hypersensitive to a wide variety of genotoxins that stall or block replication forks, and are severely defective in …
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Genetic interactions of repriming and translesion synthesis
… known eukaryotic primase outside of the core replisome. It has been previously shown to restart DNA synthesis past replication impediments such as DNA damage or non-B-DNA secondary structures. To probe the genetic interactions of PRIMPOL, genome-wide CRISPR/Cas9 knockout screens were …
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Characterisation of non-essential genes required for survival under conditions of DNA stress
… interactions, the association of Rad4 with the replisome which in turn should provide a more robust understanding of the pathways associated. Ultimately, this will serve as a platform for targeting these pathways for anti-cancer drug development.
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Structural Studies of Three Factors That Affect the Prokaryotic Transcription Cycle; Microcin J25, LAMBDA Q and T4 GP33
… and the DNA-bound sliding clamp of the T4 DNA replisome, Gp45. We obtained crystals of Gp33 bound to the Ec Beta flap that diffracted to 3.0 Ångstroms. The preliminary structure shows Gp33 as a mainly helical protein that wraps around the Beta flap.</p>
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The Roles of the Mcm2-7 Tails in Replication Initiation
… complex formation is followed by DNA unwinding, replisome assembly, DNA synthesis, and finally replication termination. The Mcm2-7 helicase is involved in every step of this process, from the earliest stages of replication initiation to the final step of replication termination. The Mcm2-7 …
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