Oxidative DNA damage: from lesion chemistry to biological implications
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | German |
| Veröffentlicht: |
München
Dr. Hut
2012
|
| Ausgabe: | 1. Aufl. |
| Schriftenreihe: | Organische Chemie
|
| Schlagworte: | |
| Online-Zugang: | Inhaltstext Inhaltsverzeichnis |
| Beschreibung: | IV, 144 S. graph. Darst. 210 mm x 148 mm, 254 g |
| ISBN: | 9783843905541 3843905541 |
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Datensatz im Suchindex
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IMAGE 1
TABLE O F CONTENTS
TABLE O F CONTENTS
TABLE O F CONTENTS I
SUMMARY 1
PART I: INTRODUCTION 7
1. INTRODUCTION TO OXIDATIVE DNA DAMAGE: PERSPECTIVES IN CHEMISTRY AND
BIOLOGY 7
1.1 DNA DAMAGE: SOURCES AND CONSEQUENCES 7
1.2 OXIDATION O F 2'-DEOXYGUANOSINE; A GENERAL VIEW 9
1.3 GUANINE OXIDATION BY "OH RADICALS 9
1.4 OXIDATION O F DG AND 8-OXO-DG BY SINGLET OXYGEN 11
1.5 OXIDATION O F DG BY ELECTRON TRANSFER: ONE AND TWO ELECTRON
REACTIONS 14
1.6 OXIDATION O F 8-OXO-DG BY ELECTRON TRANSFER 21
2. REPAIR O F OXIDATIVE DNA DAMAGE 26
2.1 BASE EXCISION REPAIR (BER) 26
2.2 DNA GLYCOSYLASES 28
2.3 THE OGG1 PROTEIN 30
3. BIOLOGICAL IMPLICATIONS O F OXIDATIVE DNA DAMAGE AS REFLECTED BY
8-OXO-DG 31
3.1 REMOVAL O F 8-OXO-DG FROM MAMMALIAN CHROMOSOMAL DNA AND OGG1 31
3.2 ABSENCE O F TIMELY REPAIR IN REPLICATION AND 8-OXO-DG 31
3.3 ABSENCE O F TIMELY REPAIR IN TRANSCRIPTION: TRANSCRIPTION COUPLED
REPAIR (TCR)
34
PART II: AIMS O F THIS WORK
PART III: RESULTS AND DISCUSSION
39
41
I
HTTP://D-NB.INFO/1025018125
IMAGE 2
TABLE O F CONTENTS
4. DERIVATIZATION O F OXIDATIVE LESIONS AND EFFECT IN STABILITY 41
4.1 PROJECT BACKGROUND 41
4.2 SYNTHESIS O F CARBOCYCLIC DEOXYGUANOSINE (CG) 42
4.3 INCORPORATION O F CG INTO DNA 44
4.4 PHOTO-OXIDATION O F DG AND CG 46
4.5 CLZ IN DOUBLE STRANDED DNA. CRYSTALLIZATION ATTEMPTS WITH A DNA
REPAIR
ENZYME 52
4.6 CARBOCYCLIC DERIVATIZATION O F DLZ ENHANCES INSTABILITY 54
4.7 THE DECOMPOSITION PATHWAY O F DLZ 57
5. THE OXIDATIVE DECOMPOSITION O F 2'-DEOXYGUANOSINE INDUCES BASE
MISINCORPORATION
BY REPLICATIVE POLYMERASES 66
5.1 MUTAGENICITY ASSAY AND PYROSEQUENCING 66
5.2 EFFECT O F THE DG - DLZ - * DZ - * DGF PATHWAY ON REPLICATIVE
POLYMERASES . 70
5.3 CONCLUSIONS 72
6. OXIDATIVE LESIONS AND TRANSCRIPTION 74
6.1 TRANSCRIPTION INHIBITION AND 8-OXO-DG: THE BACKGROUND 74
6.2 DESIGN AND CONSTRUCTION OFPLASMID SUBSTRATES CONTAINING A SINGLE
8-OXO-DG 76
6.3 THE EFFECT O F 8-OXO-DG IN TRANSCRIPTION INHIBITION 76
6.4 CONCLUSIONS 78
PART IV: EXPERIMENTAL SECTION 81
7. EXPERIMENTAL PART 81
7.1 GENERAL METHODS 81
II
IMAGE 3
TABLE O F CONTENTS
7.2 HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) 82
7.3 HPLC-ELECTROSPRAY IONIZATION MASS SPECTROMETRY (HPLC-ESI-MS) 83
7.4 ENZYMATIC DIGESTION EXPERIMENTS 83
7.5 MATRIX ASSISTED LASER DISTORTION IONIZATION MASS SPECTROMETRY
(MALDI-MS)
84
7.6 SOLID PHASE DNA SYNTHESIS 84
7.7 DEPROTECTION AND PURIFICATION O F OLIGONUCLEOTIDES 85
7.8 DNA MELTING TEMPERATURES 85
7.9 CIRCULAR DICHROISM SPECTROMETRY 86
7.10 PRIMER EXTENSION EXPERIMENTS AND DENATURING POLYACRYLAMIDE GEL
ELECTROPHORESIS 86
7.11 PYROSEQUENCING ANALYSIS 86
7.12 DNA PHOTO-OXIDATION - SYNTHESIS O F DLZ CONTAINING OLIGONUCLEOTIDES
88
7.13 SYNTHESIS O F DZ CONTAINING OLIGONUCLEOTIDES 88
7.14 SYNTHESIS O F DGF CONTAINING OLIGONUCLEOTIDES 90
7.15 EXPERIMENTS WITH DG OXIDATIVE LESIONS AT THE NUCLEOSIDE LEVEL 92
7.16 OLIGONUCLEOTIDE STABILITY EXPERIMENTS 93
7.17 ANNEALING METHODS FOR DSDNA CONTAINING ULTRASENSITIVE MODIFICATIONS
. 96
7.18 ENZYMES OVEREXPRESSION AND PURIFICATION GEOBACILLUS
STEAROTHERMOPHILUS
POLYMERASE 1 (TOPOLI) 268 97
7.19 CRYSTALLIZATION O F PROTEIN-DNA COMPLEXES 100
7.20 BIOCHEMICAL EXPERIMENTS 101
7.21 SYNTHESIS 102
III
IMAGE 4
TABLE O F CONTENTS
7.21.1 SYNTHESIS O F A CARBOCYCLIC ANALOGUE O F 2'-DEOXYGUANOSINE 102
7.21.2 SYNTHESIS O F A PROTECTED 2'-DEOXYGUANOSINE FOR THE STUDY O F ITS
OXIDATIVE
DEGRADATION PATHWAY 116
8. LITERATURE 117
9. ABBREVIATIONS 141
10. CURRICULUM VITAE 143
I V |
| any_adam_object | 1 |
| author | Stathis, Dimitrios |
| author_facet | Stathis, Dimitrios |
| author_role | aut |
| author_sort | Stathis, Dimitrios |
| author_variant | d s ds |
| building | Verbundindex |
| bvnumber | BV040389072 |
| ctrlnum | (OCoLC)812247362 (DE-599)DNB1025018125 |
| dewey-full | 572.86 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 572 - Biochemistry |
| dewey-raw | 572.86 |
| dewey-search | 572.86 |
| dewey-sort | 3572.86 |
| dewey-tens | 570 - Biology |
| discipline | Chemie / Pharmazie Biologie |
| edition | 1. Aufl. |
| format | Thesis Book |
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| spelling | Stathis, Dimitrios Verfasser aut Oxidative DNA damage from lesion chemistry to biological implications Dimitrios Stathis 1. Aufl. München Dr. Hut 2012 IV, 144 S. graph. Darst. 210 mm x 148 mm, 254 g txt rdacontent n rdamedia nc rdacarrier Organische Chemie Zugl.: München, Univ., Diss., 2012 DNS-Schädigung (DE-588)4150350-8 gnd rswk-swf Oxidativer Stress (DE-588)4353497-1 gnd rswk-swf Ringförmige DNS (DE-588)4300405-2 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Ringförmige DNS (DE-588)4300405-2 s DNS-Schädigung (DE-588)4150350-8 s Oxidativer Stress (DE-588)4353497-1 s DE-604 X:MVB text/html http://deposit.dnb.de/cgi-bin/dokserv?id=4098992&prov=M&dok_var=1&dok_ext=htm Inhaltstext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025242447&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
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| title | Oxidative DNA damage from lesion chemistry to biological implications |
| title_auth | Oxidative DNA damage from lesion chemistry to biological implications |
| title_exact_search | Oxidative DNA damage from lesion chemistry to biological implications |
| title_full | Oxidative DNA damage from lesion chemistry to biological implications Dimitrios Stathis |
| title_fullStr | Oxidative DNA damage from lesion chemistry to biological implications Dimitrios Stathis |
| title_full_unstemmed | Oxidative DNA damage from lesion chemistry to biological implications Dimitrios Stathis |
| title_short | Oxidative DNA damage |
| title_sort | oxidative dna damage from lesion chemistry to biological implications |
| title_sub | from lesion chemistry to biological implications |
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