Studies of DNA repair strategies in response to complex DNA damages
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
The main aim of this thesis was to study the role of the indirect actions of γ-rays and α-particles on the complexity of primary DNA damages and the repair fidelity of major DNA repair pathways: non-homologous end joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER). The complexity of radiation-induced damages increases and the proximity between damages decreases with increasing LET due to formation of ionization clusters along the particle track. The complexity of damages formed can be modified by the free radical scavenger dimethyl sulfoxide (DMSO). In addition, the effects of low doses of low dose rate γ-radiation on cellular response in terms of differentiation were investigated.
Paper I investigates the role of the indirect effect of radiation on repair fidelity of HRR, NHEJ and BER when damages of different complexity were induced by radiation or by potassium bromate. We found that potassium bromate induces complex DNA damages through processing of base modifications and that the indirect effect of radiation has a high impact on the NHEJ pathway. Results in paper II confirmed our conclusions in paper I that the indirect effect from both γ-rays and α-particles has an impact on all three repair pathways studied and NHEJ benefits the most when the indirect effect of radiation is removed.
In paper III we investigated the effects of low dose/dose rate γ-radiation on the developmental process of neural cells by using cell models for neurons and astrocytes. Our results suggest that low dose/dose rate γ-radiation attenuates differentiation and down-regulates proteins involved in the differentiation process of neural cells by an epigenetic rather than cytotoxic mechanism.
Place, publisher, year, edition, pages
Department of Genetics, Microbiology and Toxicology, Stockholm University , 2012. , 41 p.
ionizing radiation, complex DNA damage, indirect effect of radiation, dimethyl sulfoxide
Research subject Molecular Genetics
IdentifiersURN: urn:nbn:se:su:diva-72472ISBN: 978-91-7447-456-5OAI: oai:DiVA.org:su-72472DiVA: diva2:503576
2012-03-23, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Stenerlöw, Bo, Professor
Harms-Ringdahl, Mats, Professor
At the time of doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.2012-03-012012-02-132012-12-14Bibliographically approved
List of papers