Modulation of Base Excision Repair by Nucleosomes
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Modulation of Base Excision Repair by Nucleosomes
Modulation of Base Excision Repair by Nucleosomes
University of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by Nu Modulation of Base Excision Repair by NucleosomesucleosomesIan OdellL'nnmifv of VermontFollow this and additional works at: https://scholarworks.uvm.edu/graddisRecommended CitationOdell, lan. ’Modulation of Rase Excision Repair by Nucleosomes' (2010). Graduate Colkgt Disertuftons urn# Jtaws. 170.https: .•7scholarworks.uvm.edu /graddis/170'I his Dt Modulation of Base Excision Repair by Nucleosomessscrution rt brought to you for free JISJ open access by the Dissertations and Theses at ScholarWurks iẠ UVM. It has been accepted for inclusion in GrModulation of Base Excision Repair by Nucleosomes
aduate College Dissertations and Thews by an authorâed administrator of SiholarUbrks tỉ UVM. Foe more infoemation. please contact donrM.venalleyVẶhivmUniversity of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by Nu Modulation of Base Excision Repair by NucleosomesmontIn Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Specializing in Microbiology and Molecular GeneticsJanuary, 2011Accepted by the Faculty of the Graduate College, The University of Vermont, In partial fulfillment of the requirements for the degree of Doctor of Phi Modulation of Base Excision Repair by Nucleosomeslosophy, specializing In Microbiology and Molecular Genetics.Dissertation Examination Committee:Susan s. Wallace. PhDDate: October 20, 2010ABSTRACTDNAModulation of Base Excision Repair by Nucleosomes
in eukaryotes IS packaged into nucleosomes, which present steric impediments to many of the factors and enzymes that act on DNA. including DNA repairUniversity of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by Nu Modulation of Base Excision Repair by Nucleosomesarious chemical agents. Oxidatively damaged DNA IS repaired in a stepwise fashion via the base excision repair (BER) pathway. Other DNA repair pathways, including Nucleotide Excision Repair (NER). Mismatch Repair (MMR). Homologous Recombination (HR), and Non-homologous End-Joining (NHEJ) are all tho Modulation of Base Excision Repair by Nucleosomesught to require nucleosome remodeling or disruption. In contrast. It was reported that the first step of BER does not require or induce nucleosome disModulation of Base Excision Repair by Nucleosomes
ruption. For example, the human DNA glycosylase hNTH1 (human Endonuclease III) was discovered to excise thymine glycol lesions from nucleosomes withouUniversity of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by Nu Modulation of Base Excision Repair by Nucleosomesrson 2007). To determine if the properties of hNTH1 are shared by other human DNA glycosylases. we compared hNTH1 with NEIL1, a human DNA glycoylase that also excises thymine glycol from DNA. with respect to their activities on nucleosome substrates. We found that the cellular concentrations and app Modulation of Base Excision Repair by Nucleosomesarent kC9ỊỈKu ratios for hNTH1 and NEIL1 are similar. However. NEIL1 and hNTH1 differ in that NEIL1 binds undamaged DNA far more avidly than hNTH1. AfModulation of Base Excision Repair by Nucleosomes
ter adjustment for non-specific DNA binding. hNTH1 and NEIL1 proved to have similar intrinsic activities towards nucleosome substrates. We next wantedUniversity of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by Nu Modulation of Base Excision Repair by Nucleosomesith model, lesion-containing nucleosomes. The rates of substrate processing during the first three steps in BER. catalyzed by a DNA glycosylase. AP endonuclease, and DNA Polymerase p (Pol P). varied with the helical orientation of the substrate relative to the underlying histone octamer. In contrast Modulation of Base Excision Repair by Nucleosomes, the rate of action by DNA Ligase lll-a (in association with XRCC1) was independent of lesion orientation. These results are consistent with structurModulation of Base Excision Repair by Nucleosomes
al studies of BER enzymes and the previously proposed DNA unwrapping model for how BER enzymes gain access to lesions in nucleosomes (Prasad, Wallace,University of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by Nu Modulation of Base Excision Repair by Nucleosomest enhances the repair of lesions in nucleosomes. Together, our results support the hypothesis that DNA glycosylases have evolved to function in specific cellular environments (eg. NEIL1 may function exclusively during DNA replication), but also possess DNA binding motifs and mechanisms of substrate Modulation of Base Excision Repair by Nucleosomesrecognition that impart a similar intrinsic activity on nucleosomes. In addition to hNTH1 and NEIL1, we have discovered that lesion orientation is alsModulation of Base Excision Repair by Nucleosomes
o an important factor to the activities of APE and Pol p and that the complete BER reaction can occur without requiring or inducing nucleosome disruptUniversity of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by Nu Modulation of Base Excision Repair by NucleosomesNSMaterial from this dissertation has been published in the following form:Odell I.D.. Newick K. Heintz N H., Wallace s s.. Pederson D s.. (2010). Non-specific DNA binding interferes with the efficient excision of oxidative lesions from chromatin by the human DNA glycosylase. NEIL1. DNA Repair, 9,13 Modulation of Base Excision Repair by Nucleosomes4-143ilACKNOWLEDGEMENTSUniversity of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by NuUniversity of VermontScholarWorks (a) UVMGraduate College Dissertations and ThesesDissertations and Theses2010Modulation of Base Excision Repair by NuGọi ngay
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