Digital Public Defence: Penelope Kroustallaki
M.Sc Pinelopi Kroustallaki at Institute of Clinical Medicine will be defending the thesis “Functions of SMUG1 and NEIL3 in telomere homeostasis” for the degree of PhD (Philosophiae Doctor).
Photo: Lisa Lirussi.
The University of Oslo is closed and the public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Digital Trial Lecture – time and place
- First opponent: Professor Patricia Lynn Opresko, University of Pittsburgh
- Second opponent: Associate professor Marianne Farnebo, Karolinska Institute
- Third member and chair of the evaluation committee: Associate Professor Stephan Brackmann, University of Oslo
Chair of the Defence
Professor II Vegard Bruun Bratholm Wyller, University of Oslo
Professor Hilde Loge Nilsen, University of Oslo
Telomeres are nucleoprotein structures located at the end of chromosomes. Telomere length and the enzyme responsible for their elongation, telomerase, are essential for genome integrity by protecting chromosomal ends. Telomeric homeostasis is important in human aging and cancer and its dysfunctions is related to several diseases, from premature aging syndromes to atherosclerosis. Several factors affect telomeres, such as lifestyle, genetics, environmental agents and oxidative stress. Cells have developed mechanism to cope with DNA damage induced at telomeres e.g. by oxidative stress. One of these mechanisms is Base Excision Repair (BER). Several DNA glycosylases acting in the BER pathway have telomeric DNA as substrates. The current study was focused on the possible roles of the SMUG1 and NEIL3 DNA-glycosylases in telomeric homeostasis in human cells and mice.
This work unveils a new role of SMUG1 in the processing of the telomerase RNA component. We show that in human cells, SMUG1, via modifying bases in the hTERC sequence, ensures proper telomerase assembly. In mice, however, SMUG1 seems to predominantly function as a canonical BER DNA-glycosylase. Smug1-/- mice present tissue specific telomere defects suggesting a connection of the SMUG1 role in telomeric DNA, with senescence driven tissue aging phenotypes. A focal point of this study was also the NEIL3 DNA-glycosylase and how its function on telomeres is associated with atherosclerosis. We show that NEIL3 deficient mice present telomere erosion, which is believed to be a consequence of the overall NEIL3 deficiency as a DNA repair protein.
Overall, this data support an important role of DNA glycosylase in telomere homeostasis, by either facilitating telomerase biogenesis or by functioning as canonical BER DNA-glycosylases.
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