Ubiquitin-dependent regulation of DNA repair and apoptosis:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Mikrofilm Buch |
| Sprache: | English |
| Veröffentlicht: |
Köln
2016
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | 2 Mikrofiches (XII, 97 Seiten) Diagramme |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV044264599 | ||
| 003 | DE-604 | ||
| 005 | 00000000000000.0 | ||
| 007 | hu|uuuuuuuuuu | ||
| 007 | he|uuuuuuuuuu | ||
| 008 | 170407s2016 gw |||| bm||| 00||| eng d | ||
| 016 | 7 | |a 1128236788 |2 DE-101 | |
| 035 | |a (OCoLC)1159384616 | ||
| 035 | |a (DE-599)DNB1128236788 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c XA-DE-NW | ||
| 049 | |a DE-355 | ||
| 100 | 1 | |a Ackermann, Leena |d 1986- |e Verfasser |0 (DE-588)1122232446 |4 aut | |
| 245 | 1 | 0 | |a Ubiquitin-dependent regulation of DNA repair and apoptosis |c vorgelegt von Leena Ackermann |
| 264 | 1 | |a Köln |c 2016 | |
| 300 | |a 2 Mikrofiches (XII, 97 Seiten) |b Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b h |2 rdamedia | ||
| 338 | |b he |2 rdacarrier | ||
| 340 | |f 24x | ||
| 502 | |b Dissertation |c Universität zu Köln |d 2016 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u http://d-nb.info/1128236788/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029669405&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-029669405 | ||
Datensatz im Suchindex
| _version_ | 1804177443929456640 |
|---|---|
| adam_text | Titel: Ubiquitin-dependent regulation of DNA repair and apoptosis
Autor: Ackermann, Leena
Jahr: 2016
Table of contents
Abbreviations...............................................................................................................VIII
List of tables...................................................................................................................XI
List of figures................................................................................................................XII
1. Introduction.........................................................................................................1
1.1 The ubiquitin conjugation system and its role in regulation of cellular
processes................................................................................................2
1.1.1 Different groups of E3 ubiquitin ligases carry out substrate
ubiquitylation..................................................................................4
1.1.2 Ubiquitin ligases of the UFD pathway.............................................4
1.1.2.1 E3 ligases HECD-1 and EEL-1...........................................................5
1.1.2.2 E4 ligase UFD-2.................................................................................5
1.1.3 DUBs..............................................................................................6
1.1.4 CDC-48 - the master regulator in the ubiquitylation pathway........7
1.1.5 Ubiquitin chain editing....................................................................9
1.1.6 Proteasomal degradation...............................................................9
1.2 DNA damage response.........................................................................10
1.2.1 DNA double strand breaks...........................................................11
1.2.1.1 NHEJ................................................................................................11
1.2.1.2 Homologous recombination..............................................................12
1.2.2 Global response following DNA damage......................................14
1.2.3 Ubiquitin in homologous recombination........................................15
1.2.4 DNA damage response in C. elegans..........................................16
1.3 Apoptosis...............................................................................................17
1.3.1 Ubiquitin-dependent apoptosis regulation....................................17
1.3.2 Apoptosis in C. elegans................................................................18
1.4 Communication between DNA damage repair and apoptosis...............19
1.5 Aims of this study..................................................................................20
2. Results...............................................................................................................21
2.1 UFD-2 acts specifically in DNA damage induced apoptosis..................22
2.2 Apoptosis activation via CEP-1 is normal upon loss of ufd-2................24
2.3 UFD-2 foci are dependent on CEP-1 signalling.....................................24
2.4 UFD-2 is required for completion of DNA damage repair......................26
2.5 Active DNA repair is required for UFD-2 foci formation.........................29
2.6 Catalytic activity of UFD-2 is required for DNA damage repair and
damage induced apoptosis....................................................................30
2.7 UFD-2 defines hubs harbouring components of the proteolytic system 32
2.7.1 UFD-2 foci accumulate within nucleoli..........................................32
2.7.2 Ubiquitin accumulates in UFD-2 hubs..........................................33
2.7.3 CDC-48 accumulates in ubiquitylation hubs.................................33
2.8 CDC-48 in DNA repair and apoptosis....................................................34
2.8.1 UFD-2 interaction with the ubiquitin-directed segregase CDC-48
is required for DNA damage induced apoptosis..........................34
2.8.2 CDC-48 in DNA repair..................................................................35
2.9 The E3 ligase HECD-1 is required for UFD-2 foci formation.................36
2.10 Degradation hubs include DNA repair proteins.....................................37
2.11 Identification of accessory factors contributing to DNA damage
response...............................................................................................38
2.11.1 RNAi screen to identify DUBs that genetically interact with
UFD-2.........................................................................................38
2.11.2 Selected candidates...................................................................39
2.11.2.1 ubh-2 and ubh-3.............................................................................39
2.11.2.2 atx-3................................................................................................40
2.12 DNA associated RAD-51 inhibits apoptosis execution..........................42
3. Discussion.........................................................................................................45
3.1 Identification of UFD-2 as an essential player in DSB response...........46
3.2 UFD-2 defines ubiquitylation hubs after DSB formation........................47
3.3 Functional relevance of UFD-2-defined degradation hubs for efficient
DSB repair.............................................................................................48
3.4 UFD-2 connects efficient DSB repair to apoptosis commitment............50
3.5 Putative role of UFD-2 in the apoptotic signalling cascade...................51
3.6 Coordination of DSB repair and apoptosis signalling via UFD-2...........52
3.7 RAD-51 filaments as determinant of repair vs. apoptosis.....................53
4. Methods..............................................................................................................56
4.1 Resources and software........................................................................57
4.1.1 Consumables, reagents, and instruments....................................57
4.1.2 Software, databases, and resources............................................57
4.1.3 Antibodies.....................................................................................58
4.2 Microbiology..........................................................................................59
4.2.1 Solutions and media.....................................................................59
4.2.2 Antibiotics.....................................................................................60
4.2.3 Bacterial strains............................................................................60
4.2.4 Cultivation of bacteria...................................................................60
4.2.5 Manufacturing of chemo-competent E. coli..................................60
4.2.6 Transformation of chemo-competent E. coli.................................61
4.3 Molecular Biology..................................................................................61
4.3.1 Solutions.......................................................................................61
4.3.3 Primer...........................................................................................61
4.3.4 Isolation of plasmid DNA from bacteria........................................62
4.3.5 Agarose Gel electrophoresis........................................................62
4.3.6 Polymerase Chain reaction (PGR)...............................................63
4.4 Caenorhabditis elegans specific methods.............................................63
4.4.1 Solutions and media.....................................................................63
4.4.2 C. elegans strains.........................................................................65
4.4.3 Synchronization of worm cultures.................................................66
4.4.4 Growing worms in liquid cultures..................................................67
4.4.5 Single worm lysis for genotyping..................................................67
4.4.6 RNAi treatment.............................................................................67
4.4.7 RNA isolation and real-time PCR.................................................67
4.4.8 Ionizing radiation..........................................................................68
4.4.9 Apoptosis assay...........................................................................68
4.4.10 Immunotechniques.....................................................................68
4.4.11 UFD-2 foci..................................................................................69
4.4.12 Persistence of RAO-SI foci after IR............................................69
4.4.13 Embryonic Survival.....................................................................69
4.4.14 B02 treatment.............................................................................69
4.4.15 Mitotic germ cell cycle arrest upon IR.........................................69
4.5 Microscopy and image acquisition.........................................................70
4.6 Statistical analysis.................................................................................70
References..................................................................................................................71
Appendix.....................................................................................................................92
Appendix A: Evaluation of RNAi screen................................................92
Appendix B: Table with selected candidates.........................................92
Danksagung................................................................................................................95
Curriculum vitae.........................................................................................................96
Erklarung.....................................................................................................................97
|
| any_adam_object | 1 |
| author | Ackermann, Leena 1986- |
| author_GND | (DE-588)1122232446 |
| author_facet | Ackermann, Leena 1986- |
| author_role | aut |
| author_sort | Ackermann, Leena 1986- |
| author_variant | l a la |
| building | Verbundindex |
| bvnumber | BV044264599 |
| ctrlnum | (OCoLC)1159384616 (DE-599)DNB1128236788 |
| format | Thesis Microfilm Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01309nam a2200337 c 4500</leader><controlfield tag="001">BV044264599</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">00000000000000.0</controlfield><controlfield tag="007">hu|uuuuuuuuuu</controlfield><controlfield tag="007">he|uuuuuuuuuu</controlfield><controlfield tag="008">170407s2016 gw |||| bm||| 00||| eng d</controlfield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">1128236788</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1159384616</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DNB1128236788</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="044" ind1=" " ind2=" "><subfield code="a">gw</subfield><subfield code="c">XA-DE-NW</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-355</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Ackermann, Leena</subfield><subfield code="d">1986-</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1122232446</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Ubiquitin-dependent regulation of DNA repair and apoptosis</subfield><subfield code="c">vorgelegt von Leena Ackermann</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Köln</subfield><subfield code="c">2016</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">2 Mikrofiches (XII, 97 Seiten)</subfield><subfield code="b">Diagramme</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">h</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">he</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="340" ind1=" " ind2=" "><subfield code="f">24x</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="b">Dissertation</subfield><subfield code="c">Universität zu Köln</subfield><subfield code="d">2016</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">B:DE-101</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://d-nb.info/1128236788/04</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029669405&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-029669405</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV044264599 |
| illustrated | Not Illustrated |
| indexdate | 2024-07-10T07:48:10Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-029669405 |
| oclc_num | 1159384616 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | 2 Mikrofiches (XII, 97 Seiten) Diagramme |
| publishDate | 2016 |
| publishDateSearch | 2016 |
| publishDateSort | 2016 |
| record_format | marc |
| spelling | Ackermann, Leena 1986- Verfasser (DE-588)1122232446 aut Ubiquitin-dependent regulation of DNA repair and apoptosis vorgelegt von Leena Ackermann Köln 2016 2 Mikrofiches (XII, 97 Seiten) Diagramme txt rdacontent h rdamedia he rdacarrier 24x Dissertation Universität zu Köln 2016 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf http://d-nb.info/1128236788/04 Inhaltsverzeichnis HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029669405&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Ackermann, Leena 1986- Ubiquitin-dependent regulation of DNA repair and apoptosis |
| subject_GND | (DE-588)4113937-9 |
| title | Ubiquitin-dependent regulation of DNA repair and apoptosis |
| title_auth | Ubiquitin-dependent regulation of DNA repair and apoptosis |
| title_exact_search | Ubiquitin-dependent regulation of DNA repair and apoptosis |
| title_full | Ubiquitin-dependent regulation of DNA repair and apoptosis vorgelegt von Leena Ackermann |
| title_fullStr | Ubiquitin-dependent regulation of DNA repair and apoptosis vorgelegt von Leena Ackermann |
| title_full_unstemmed | Ubiquitin-dependent regulation of DNA repair and apoptosis vorgelegt von Leena Ackermann |
| title_short | Ubiquitin-dependent regulation of DNA repair and apoptosis |
| title_sort | ubiquitin dependent regulation of dna repair and apoptosis |
| topic_facet | Hochschulschrift |
| url | http://d-nb.info/1128236788/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029669405&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT ackermannleena ubiquitindependentregulationofdnarepairandapoptosis |
Es ist kein Print-Exemplar vorhanden.
Inhaltsverzeichnis