NOVEL ROLE OF HEATR1 IN RIBOSOME BIOGENESIS AND DNA DAMAGE SIGNALING

Zsófia TURI, M.Sc.

Disertační práce

Anotace:

In this work, we identified a nucleolar protein, HEATR1 as an important player of ribosome biogenesis. In the absence of this protein, ribosome biogenesis stress is activated, characterized by the elevated level of p53, cell cycle arrest and structural changes of the nucleolus. Furthermore, HEATR1 seems to be involved in the early steps of ribosome biogenesis, since it possesses similar localization signal to Pol I and its ablation completely abolishes rRNA transcription. Besides its function in ribosome biosynthesis, HEATR1 may be required for DNA damage signaling as well, evidenced by DNA damage-dependent phosphorylation of this protein. Overall, our work presents HEATR1, a novel player in ribosome biogenesis and DNA damage response.

Abstract:

In this work, we identified a nucleolar protein, HEATR1 as an important player of ribosome biogenesis. In the absence of this protein, ribosome biogenesis stress is activated, characterized by the elevated level of p53, cell cycle arrest and structural changes of the nucleolus. Furthermore, HEATR1 seems to be involved in the early steps of ribosome biogenesis, since it possesses similar localization signal to Pol I and its ablation completely abolishes rRNA transcription. Besides its function in ribosome biosynthesis, HEATR1 may be required for DNA damage signaling as well, evidenced by DNA damage-dependent phosphorylation of this protein. Overall, our work presents HEATR1, a novel player in ribosome biogenesis and DNA damage response.

Klíčová slova

Ribosome biogenesis, nucleolus, HEATR1, p53, cancer, DNA damage response

Jazyk práce: čeština

Datum vytvoření / odevzdání či podání práce: 30. 4. 2019

Obhajoba závěrečné práce

• Obhajoba proběhla 26. 11. 2019
• Vedoucí: Ing. Pavel Moudrý, Ph.D.

UNIVERZITA PALACKÉHO V OLOMOUCI

Lékařská fakulta

Doktorský studijní program / obor:
Pediatrie / Pediatrie