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Showing 1 to 20 of 33 for “"translesion synthesis"”.
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Genetic interactions of repriming and translesion synthesis
… 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 undertaken in the human TK6 cell line. The most interesting …
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DNA polymerase interactions and their role In translesion synthesis substitutions.
Translesion synthesis (TLS) is a DNA damage tolerance mechanism that allows DNA replication to continue after a high fidelity (HiFi) polymerase stalls at a lesion. Upon stalling, the HiFi polymerase must be substituted with a TLS polymerase. The reverse substitution must occur promptly after lesion …
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Single-molecule studies of bacterial DNA replication and translesion synthesis
… blocks, cells harbor multiple specialized translesion DNA polymerases that are error-prone and therefore able to accommodate the lesions and continue DNA synthesis. As a result of their low fidelity, the translesion polymerases are associated with increased mutagenesis, drug resistance, and …
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DNA Translesion Synthesis Factors are Essential for Mammalian Embryonic Germ Cell Development
… the action of error-prone pathways such as DNA translesion synthesis (TLS). TLS enables DNA replication to be completed when the replication machinery stalls at impediments. In order to bypass these blocks, specialised factors are employed to ensure the completion of replication. However, due to …
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Regulation of DNA damage tolerance : studies of the translesion synthesis DNA ploymerase eta in Saccharomyces cerevisiae
… presence of DNA damage. One such mechanism is translesion synthesis (TLS), in which a specialized polymerase replicates a damaged DNA template. These studies address the regulation of the eukaryotic TLS polymerase eta, which is particularly important for accurately bypassing UV-induced DNA …
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Structure-Based Drug Design in Medicinal Chemistry I. Development of Translesion Synthesis Inhibitors II. Synthesis and Biological Evaluation of Sulfonyl Piperazine Derivatives for LpxH Inhibition
… details studies of the development of translesion synthesis (TLS) inhibitors. Translesion synthesis is a major mechanism to enable bypass replication over DNA lesions. Lesion bypass is carried out by specialized TLS polymerases that use damaged DNA as templates and insert nucleotides …
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Mechanism of Mismatch Repair Induced Mutagenesis in Somatic Hypermutation
… and Exo1, but is additionally dependent upon the translesional DNA polymerase eta, a known A:T mutator, and on ubiquitinated PCNA, an initiator of translesion synthesis. The presence of certain types of lesions in the template strand during DNA replication leads to the activation of translesion …
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Analysis of NusA's roles in DNA repair and damage tolerance pathways in Escherichia coli
… as a coupling factor in transcription-coupled translesion synthesis (TC-TLS) and nucleotide excision repair (TCR) processes. A very recent paper by Nudler's lab further supports Cohen's NusA-dependent TCR model. The objectives of the work described here are to gain a deeper understanding of the …
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Rev7 is a novel regulator of chemotherapeutic response in drug-resistant lung cancer
… relevance of that Rev7, a multi-functional translesion synthesis (TLS) DNA damage tolerance protein in drug-resistant cancers.
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Translesion synthesis and mutations: On the mutagenic properties of the two DNA lesions, 8-oxo-G and Pt-GG, and the functions of Y-family DNA polymerases and Rev3L on the bypass of each of the DNA lesions in mammalian cells
… I deduced the biological functions of the translesion DNA polymerases Pol eta, Pol kappa, Pol iota, Rev1 and Rev3L on bypassing each of the lesions 8-oxo-G and Pt-GG. My study takes advantage of the Next Generation Sequencing (NGS) technology to determine mutagenic effects of the DNA …
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Role of TLS Polymerases in Replication of DNA Lesions in Human Cells
… DNA damage tolerance mechanisms, including translesion synthesis (TLS), alleviate this block at the expense of increasing mutagenesis. Minor groove DNA lesions result from lipid peroxidation or exposure to environmental pollutants. Prevalent among these lesions are those produced by tobacco …
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Novel function and regulation of mutagenic DNA polymerases in Escherichia coli
… DNA polymerases with the ability to catalyze synthesis on imperfect DNA templates in a process termed translesion synthesis (TLS). Similar enzymes exist in nearly all organisms, constituting the Y-superfamily of DNA polymerases. Although DinB is the only Y-family DNA polymerase conserved among …
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Chemistry and Biology of DNA-protein cross-links
… site-specific DPCs were subjected to in vitro translesion synthesis (TLS) in the presence of TLS DNA polymerases. We found that DPCs containing various full-length proteins conjugated to DNA via the C-5 position of cytosine completely blocked human DNA polymerases, while the corresponding …
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Protein and Ligand Dynamics in Drug Development and Resistance
… and optimization of an inhibitor targeting translesion synthesis, a process that cancer cells can employ to resist the killing action of chemotherapeutics. Early work on this project demonstrated that inhibition of Rev1, an important scaffold in the translesion synthesis process, by the …
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The Apollo Nuclease Binds To TRF2 and Protects
… with Apollo and localizes to Cajal bodies, the translesion synthesis polymerase polη, and the homolgous recombination factor Rad51. The association of these proteins with Apollo suggests potential roles for Apollo in telomerase recruitment and formation of the protective t-loop structure at …
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Identification and Characterization of Modulators of Chemotherapeutic Response in Mouse Models of Cancer
… vivo chemotherapeutic response. By suppressing translesion synthesis, initially in Bcell lymphoma and later in a newly developed transplantable model of murine lung adenocarcinoma, I show that tumors are not only sensitized to clinically relevant chemotherapeutics, but are also partially …
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The identification of novel factors required for the development of primordial germ cells
… the development of PGCLCs. We identified the translesion synthesis (TLS) factor Rev1 as a key factor involved in PGCLC development. Furthermore, we validated this requirement in vivo and showed that absence of Rev1 causes a numeric reduction in PGCs during the migratory period of PGC …
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Focused CRISPR-Cas9 screens investigating the DNA damage response
… deficient in nucleotide excision repair and translesion synthesis. We propose that increased cell survival associated with SLFN11 depletion arises from utilisation of a combination of repair pathways in which cells remain proficient, including homologous recombination and the use of …
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Lesion Bypass of N2-ethylguanine by the Human Y Family DNA Polymerases Iota and Kappa
The purpose of this work is to test the hypothesis that the human Y family DNA polymerases have a biological function in the bypass of alkylation DNA damage. The lesion bypass properties of the Y family DNA polymerases ι and κ opposite the N2-ethylGua DNA adduct were studied using steady-state and …
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Structure-Guided Design of Novel Therapeutics Targeting Translesion DNA Synthesis and Lipid A Biosynthesis
… an error-prone DNA-repair process called translesion DNA synthesis (TLS). The Rev1 polymerase orchestrates this pathway by recruiting one of three inserter polymerases and the extender polymerase (Pol ζ) to bypass the lesion. Here we report the discovery and characterization of an …
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