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- DNA mismatch repair (2)
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Articles 1 - 12 of 12
Full-Text Articles in Life Sciences
A Noncanonical Function Of The Telomerase Rna Component In Human Embryonic Stem Cells, Kirsten Ann Brenner
A Noncanonical Function Of The Telomerase Rna Component In Human Embryonic Stem Cells, Kirsten Ann Brenner
Arts & Sciences Electronic Theses and Dissertations
Telomeres are stretches of TTAGGG nucleotide repeats located at the ends of linear chromosomes that shorten with progressive cell division and prevent genomic instability at the cost of limiting a cell’s capacity to proliferate. This limitation can be overcome by telomerase, a ribonucleoprotein complex that elongates telomeres via reverse-transcription of the template telomerase RNA component (TERC). Recent studies have reported potential functions of TERC outside of its role in telomere maintenance. These noncanonical functions of TERC are however poorly defined, and the molecular mechanisms and biological relevance behind such functions remain elusive. Here, we generated conditional TERC knock-out human embryonic …
Activation And Regulation Of The Alkbh3-Ascc Alkylation Repair Pathway, Josh Brickner
Activation And Regulation Of The Alkbh3-Ascc Alkylation Repair Pathway, Josh Brickner
Arts & Sciences Electronic Theses and Dissertations
DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions. These lesions are sensed by distinct pathways to recruit repair factors specific to type of damage. In particular, the ALKBH family of proteins recognizes and repairs specific alkylated lesions, including 1-methyladenine (m1A) and 3-methylcytosine (m3C). A major outstanding question in the field is how the AlkB homologue ALKBH3 and its associated protein partners are recruited to sites of alkylation damage and how this repair activity is regulated. Understanding the upstream signaling events that mediate recognition and repair of DNA alkylation damage is particularly …
Transcriptional Regulation Of Adipose Tissue Development By Pexrap And Med19, John Dean
Transcriptional Regulation Of Adipose Tissue Development By Pexrap And Med19, John Dean
Arts & Sciences Electronic Theses and Dissertations
Targeting adipose tissue function to decrease adiposity and improve insulin sensitivity could treat obesity and diabetes. How the nuclear receptor PPARγ regulates the development of two functionally distinct types of adipose tissue, brown and white fat (BAT and WAT), as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis.Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its …
Sideromycin Pathway Elucidation: Insights Into Salmycin Biosynthesis, Transport Paradigms, And Drug Release, Gerry Sann Macaraeg Rivera
Sideromycin Pathway Elucidation: Insights Into Salmycin Biosynthesis, Transport Paradigms, And Drug Release, Gerry Sann Macaraeg Rivera
Arts & Sciences Electronic Theses and Dissertations
Antibiotic resistance is an increasing threat in today’s society. In order to overcome resistant bacteria, it is necessary to discover new drugs with novel mechanisms of action. This work focuses on the sideromycin pathway, encompassing the biosynthetic production, mechanism of entry and hydrolysis-mediated drug release. Sideromycins are an interesting approach to combat the rise of antibiotic resistance since they provide a different avenue that overcomes problems that arise when entering the cell. The dissertation is separated into distinct sections dealing with the various areas of interest in the sideromycin pathway, particularly for the sideromycin, salmycin, produced by Streptomyces violaceus. The …
Elucidating Enhancer Function In Epidermal Development And Filaggrin Loss-Of-Function Variants In African American Atopic Dermatitis, Mary Elizabeth Mathyer
Elucidating Enhancer Function In Epidermal Development And Filaggrin Loss-Of-Function Variants In African American Atopic Dermatitis, Mary Elizabeth Mathyer
Arts & Sciences Electronic Theses and Dissertations
The epidermis is the outermost tissue of the skin and provides the body’s first line of defense against external assaults. The epidermis is primarily composed of keratinocytes that terminally differentiate and rise apically toward the surface to form the semipermeable barrier of the skin. A hallmark of keratinocyte terminal differentiation is the expression of genes from the Epidermal Differentiation Complex (EDC) locus. Many of the EDC protein products contribute to the structural integrity of the skin barrier, evidenced by several gene knockouts such as loricrin, and even genetic variation within gene coding sequences, that modulate the integrity of the skin …
Investigating Biological Mechanisms Of Radiation Resistance In Advanced Stage Cervical Cancer, Fiona Ruiz
Investigating Biological Mechanisms Of Radiation Resistance In Advanced Stage Cervical Cancer, Fiona Ruiz
Arts & Sciences Electronic Theses and Dissertations
The current standard of care treatment for locally advanced cervical cancer is curative intent pelvic radiation with concurrently administered platinum chemotherapy (CRT). This treatment strategy is effective for many patients, but 33-50% of patients treated with CRT develop disease recurrence. Metastatic and recurrent cervical cancer is an incurable condition, and many of the currently available treatments are associated with significant morbidity and mortality. Identifying these patients upfront is a challenge that clinicians face when developing treatment strategies. Previous studies used to catalog the genomic and transcriptomic landscape of cervical cancer lacked high quality corresponding clinical follow up data for patients, …
Regulation Of The Yeast Cell Cycle Checkpoint Kinase Tel1 At Double-Strand Dna Breaks And At Telomeres, Sarem Hailemariam
Regulation Of The Yeast Cell Cycle Checkpoint Kinase Tel1 At Double-Strand Dna Breaks And At Telomeres, Sarem Hailemariam
Arts & Sciences Electronic Theses and Dissertations
The work discussed in this dissertation focuses on two distinct areas that are critical for genome maintenance. Both areas are focused on the regulation of the Saccharomyces cerevisiae checkpoint kinase Tel1 by the MRX complex. Tel1 kinase initiates cell cycle checkpoint in response to double-strand DNA breaks. Tel1 also plays a major role in telomere maintenance. Tel1’s function both in checkpoint signaling and telomere regulation is dependent on the Mre11-Rad50-Xrs2 complex. In Chapter II, I describe a robust biochemical approach aimed at reconstituting the initial stages of double-strand DNA break response using purified proteins in order to address how the …
The Impact Of Mrna Structure On Trna Selection And Ribosome Rescue, Erica Nicole Thomas
The Impact Of Mrna Structure On Trna Selection And Ribosome Rescue, Erica Nicole Thomas
Arts & Sciences Electronic Theses and Dissertations
The faithful and rapid translation of proteins from genetic information is an essential feature of the ribosome. The general process of tRNA selection is governed by the ability of the ribosome to select for the aminoacylated tRNA (aa-tRNA) that matches the codon in its A-site. The efficiency and accuracy of this selection depends on the ability of nucleotides to form proper hydrogen bonds. While much is known about how chemical alterations of tRNA and rRNA can impact the fidelity of translation, less is known about how similar changes to mRNA affect decoding. In this work, we describe several studies aimed …
Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev
Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev
Arts & Sciences Electronic Theses and Dissertations
E. coli UvrD is a superfamily 1A helicase/translocase involved in DNA repair, recombination, and replication. I investigated the role of E. coli MutL, a regulatory protein involved in methyl-directed mismatch DNA repair, in the regulation of UvrD-catalyzed DNA unwinding. Using single molecule fluorescence resonance energy transfer (FRET) and single round stopped-flow DNA unwinding experiments I demonstrated that MutL can activate latent UvrD monomer helicase activity and also stimulate UvrD dimer helicase activity. Furthermore, using analytical ultracentrifugation experiments I determined that a single MutL dimer is sufficient to activate UvrD monomer helicase. DNA unwinding experiments with a series of DNA substrates …
Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev
Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev
Arts & Sciences Electronic Theses and Dissertations
E. coli UvrD is a superfamily 1A helicase/translocase involved in DNA repair, recombination, and replication. I investigated the role of E. coli MutL, a regulatory protein involved in methyl-directed mismatch DNA repair, in the regulation of UvrD-catalyzed DNA unwinding. Using single molecule fluorescence resonance energy transfer (FRET) and single round stopped-flow DNA unwinding experiments I demonstrated that MutL can activate latent UvrD monomer helicase activity and also stimulate UvrD dimer helicase activity. Furthermore, using analytical ultracentrifugation experiments I determined that a single MutL dimer is sufficient to activate UvrD monomer helicase. DNA unwinding experiments with a series of DNA substrates …
The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer
The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer
Arts & Sciences Electronic Theses and Dissertations
Characteristics of breast tumor stroma, including altered collagen architecture and increased stiffness, are known to contribute to tumor invasion and metastasis. However, the cellular and molecular mechanisms by which these changes occur are not fully understood. To address this question, we used a mouse genetic model to delete Discoidin Domain Receptor 2 (DDR2) from mouse tumor stromal cells and interrogated breast cancer associated fibroblasts (CAFs) to determine the molecular events downstream of DDR2 action that may lead to changes in the tumor extracellular matrix (ECM). Our work revealed that the action of DDR2 in breast stromal cells is required for …
The Role Of Ifrd1 In The Recruitment And Function Of Reserve Stem Cells In Regeneration And Cancer, Mark Anthony Lewis
The Role Of Ifrd1 In The Recruitment And Function Of Reserve Stem Cells In Regeneration And Cancer, Mark Anthony Lewis
Arts & Sciences Electronic Theses and Dissertations
Mature cells can reprogram into a proliferative, progenitor-like state to repair tissue following injury and inflammation. Differentiated cells in diverse tissues can become proliferative via a dedicated, evolutionarily conserved program we termed paligenosis. We detailed how paligenosis occurs, in both gastric chief and pancreatic acinar cells, in a step-wise manner that involves: 1) autodegradation of mature cell components; 2) re-expression of progenitor genes; 3) re-entry into the cell cycle. This process is governed by mTORC1, a fundamental cellular energy sensor and regulator of protein translation. Blocking mTORC1 permitted autophagy and metaplastic gene induction but blocked cell cycle re-entry at S-phase. …