The biosynthesis of ribosomes is a complex process that requires the coordinated action of many factors and a huge energy investment from the cell. Ribosomes are essential for protein production, and thus for cellular survival, growth and proliferation. Ribosome biogenesis is initiated in the nucleolus and includes: the synthesis and processing of ribosomal RNAs, assembly of ribosomal proteins, transport to the cytoplasm and association of ribosomal subunits. The disruption of ribosome biogenesis at various steps, with either increased or decreased expression of different ribosomal components, can promote cell cycle arrest, senescence or apoptosis. Additionally, interference with ribosomal biogenesis is often associated with cancer, aging and age-related degenerative diseases. Here, we review current knowledge on impaired ribosome biogenesis, discuss the main factors involved in stress responses under such circumstances and focus on examples with clinical relevance.

• Klíčová slova
• aging, cancer, p53, ribosome biogenesis, ribosomopathy,
• MeSH
• biogeneze organel MeSH
• lidé MeSH
• nádory metabolismus   MeSH
• ribozomální proteiny metabolismus   MeSH
• ribozomy metabolismus   MeSH
• stárnutí metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• ribozomální proteiny MeSH

Repair of ribosomal DNA (rDNA) is a very important nuclear process due to the most active transcription of ribosomal genes. Proper repair of rDNA is required for physiological biogenesis of ribosomes. Here, we analyzed the epigenetics of the DNA damage response in a nucleolar compartment, thus in the ribosomal genes studied in nonirradiated and UVA-irradiated mouse embryonic fibroblasts (MEFs). We found that the promoter of ribosomal genes is not abundant on H4K20me2, but it is densely occupied by H4K20me3. Ribosomal genes, regulated via UBF1/2 proteins, were characterized by an interaction between UBF1/2 and H4K20me2/me3. This interaction was strengthened by UVA irradiation that additionally causes a focal accumulation of H4K20me3 in the nucleolus. No interaction has been found between UBF1/2 and H3K9me3. Interestingly, UVA irradiation decreases the levels of H3K9me3 and H4K20me3 at 28S rDNA. Altogether, the UVA light affects the epigenetic status of ribosomal genes at 28S rDNA and strengthens an interaction between UBF1/2 proteins and H4K20me2/me3.

• Klíčová slova
• DNA damage response, DNA repair, Nucleolus, UBF, UVA irradiation,
• MeSH
• buněčné jadérko metabolismus   MeSH
• buněčné jádro metabolismus   MeSH
• chromatinová imunoprecipitace MeSH
• DNA vazebné proteiny MeSH
• epigeneze genetická účinky záření   MeSH
• fluorescenční protilátková technika MeSH
• histony metabolismus   MeSH
• metylace MeSH
• myši MeSH
• promotorové oblasti (genetika) MeSH
• regulace genové exprese účinky záření   MeSH
• ribozomální DNA genetika   MeSH
• transkripční iniciační komplex Pol1 - proteiny metabolismus   MeSH
• ultrafialové záření * MeSH
• vazba proteinů MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• histony MeSH
• ribozomální DNA MeSH
• transcription factor UBF MeSH Prohlížeč
• transkripční iniciační komplex Pol1 - proteiny MeSH

DNA damage response (DDR) in ribosomal genes and mechanisms of DNA repair in embryonic stem cells (ESCs) are less explored nuclear events. DDR in ESCs should be unique due to their high proliferation rate, expression of pluripotency factors, and specific chromatin signature. Given short population doubling time and fast progress through G1 phase, ESCs require a sustained production of rRNA, which leads to the formation of large and prominent nucleoli. Although transcription of rRNA in the nucleolus is relatively well understood, little is known about DDR in this nuclear compartment. Here, we directed formation of double-strand breaks in rRNA genes with I- PpoI endonuclease, and we studied nucleolar morphology, DDR, and chromatin modifications. We observed a pronounced formation of I- PpoI-induced nucleolar caps, positive on BRCA1, NBS1, MDC1, γH2AX, and UBF1 proteins. We showed interaction of nucleolar protein TCOF1 with HDAC1 and TCOF1 with CARM1 after DNA injury. Moreover, H3R17me2a modification mediated by CARM1 was found in I- PpoI-induced nucleolar caps. Finally, we report that heterochromatin protein 1 is not involved in DNA repair of nucleolar caps.

• Klíčová slova
• CARM1, DNA repair, HDAC1, NBS1, PpoI, chromatin, nucleolus,
• MeSH
• acetylace MeSH
• arginin metabolismus   MeSH
• buněčné jadérko genetika   ultrastruktura   MeSH
• buněčné linie MeSH
• dvouřetězcové zlomy DNA * MeSH
• embryonální kmenové buňky metabolismus   ultrastruktura   MeSH
• fosfoproteiny metabolismus   MeSH
• geny rRNA MeSH
• histondeacetylasa 1 metabolismus   MeSH
• histony metabolismus   MeSH
• intracelulární signální peptidy a proteiny MeSH
• jaderné proteiny metabolismus   MeSH
• metylace MeSH
• myši MeSH
• oprava DNA MeSH
• proteinarginin-N-methyltransferasy metabolismus   MeSH
• RNA ribozomální genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• arginin MeSH
• coactivator-associated arginine methyltransferase 1 MeSH Prohlížeč
• fosfoproteiny MeSH
• Hdac1 protein, mouse MeSH Prohlížeč
• histondeacetylasa 1 MeSH
• histony MeSH
• intracelulární signální peptidy a proteiny MeSH
• jaderné proteiny MeSH
• proteinarginin-N-methyltransferasy MeSH
• RNA ribozomální MeSH
• Tcof1 protein, mouse MeSH Prohlížeč