Lilli Theres Eilertsen Bay

• Bay, Lilli Theres Eilertsen; Stokke, Trond; Syljuåsen, Randi G. & Landsverk, Helga Bjarnason (2023). Analysis of RNA Polymerase II Chromatin Binding by Flow Cytometry. Bio-protocol. 13(8). doi: 10.21769/BioProtoc.4659. Fulltekst i vitenarkiv
• Bay, Lilli Theres Eilertsen; Syljuåsen, Randi G. & Landsverk, Helga Bjarnason (2022). A novel, rapid and sensitive flow cytometry method reveals degradation of promoter proximal paused RNAPII in the presence and absence of UV. Nucleic Acids Research (NAR). ISSN 0305-1048. 50(15). doi: 10.1093/nar/gkac434. Fulltekst i vitenarkiv
• Rødland, Gro Elise; Hauge, Sissel; Hasvold, Grete; Bay, Lilli Theres Eilertsen; Henriksen-Raabe, Tine Therese & Joel, Mrinal [Vis alle 7 forfattere av denne artikkelen] (2021). Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells. Cancers. doi: 10.3390/cancers13153790. Fulltekst i vitenarkiv Vis sammendrag

  Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.

• Landsverk, Helga Bjarnason; Sandquist, Lise Ellefsen; Bay, Lilli Theres Eilertsen & Syljuåsen, Randi G. (2021). New link between the RNA polymerase II-CTD and replication stress. Molecular and Cellular Oncology (MCO). doi: 10.1080/23723556.2021.1910008. Fulltekst i vitenarkiv Vis sammendrag

  Conflicts between transcription and replication are a major source of replication stress. Our recent findings show that proper dephosphorylation of Serine 5 in the carboxy-terminal domain (CTD) of DNA-directed RNA polymerase II subunit RPB1 is needed to prevent such conflicts in human cells.

• Hauge, Sissel; Mariampillai, Adrian Eek; Rødland, Gro Elise; Bay, Lilli Theres Eilertsen; Landsverk, Helga Bjarnason & Syljuåsen, Randi G. (2021). Expanding roles of cell cycle checkpoint inhibitors in radiation oncology. International Journal of Radiation Biology. ISSN 0955-3002. doi: 10.1080/09553002.2021.1913529. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Radiation-induced activation of cell cycle checkpoints have been of long-standing interest. The WEE1, CHK1 and ATR kinases are key factors in cell cycle checkpoint regulation and are essential for the S and G2 checkpoints. Here, we review the rationale for why inhibitors of WEE1, CHK1 and ATR could be beneficial in combination with radiation. Conclusions Combined treatment with radiation and inhibitors of these kinases results in checkpoint abrogation and subsequent mitotic catastrophe. This might selectively radiosensitize tumor cells, as they often lack the p53-dependent G1 checkpoint and therefore rely more on the G2 checkpoint to repair DNA damage. Further affecting the repair of radiation damage, inhibition of WEE1, CHK1 or ATR also specifically suppresses the homologous recombination repair pathway. Moreover, inhibition of these kinases can induce massive replication stress during S phase of the cell cycle, likely contributing to eliminate radioresistant S phase cells. Intriguingly, recent findings suggest that cell cycle checkpoint inhibitors in combination with radiation can also enhance anti-tumor immune effects. Altogether, the expanding knowledge about the functional roles of WEE1, CHK1 and ATR inhibitors support that they are promising candidates for use in combination with radiation treatment.

• Landsverk, Helga Bjarnason; Sandquist, Lise Ellefsen; Bay, Lilli Theres Eilertsen; Steurer, Barbara; Campsteijn, Coen & Landsverk, Ole J. B. [Vis alle 10 forfattere av denne artikkelen] (2020). WDR82/PNUTS-PP1 Prevents Transcription-Replication Conflicts by Promoting RNA Polymerase II Degradation on Chromatin. Cell reports. 33(9). doi: 10.1016/j.celrep.2020.108469. Fulltekst i vitenarkiv Vis sammendrag

  Transcription-replication (T-R) conflicts cause replication stress and loss of genome integrity. However, the transcription-related processes that restrain such conflicts are poorly understood. Here, we demonstrate that the RNA polymerase II (RNAPII) C-terminal domain (CTD) phosphatase protein phosphatase 1 (PP1) nuclear targeting subunit (PNUTS)-PP1 inhibits replication stress. Depletion of PNUTS causes lower EdU uptake, S phase accumulation, and slower replication fork rates. In addition, the PNUTS binding partner WDR82 also promotes RNAPII-CTD dephosphorylation and suppresses replication stress. RNAPII has a longer residence time on chromatin after depletion of PNUTS or WDR82. Furthermore, the RNAPII residence time is greatly enhanced by proteasome inhibition in control cells but less so in PNUTS- or WDR82-depleted cells, indicating that PNUTS and WDR82 promote degradation of RNAPII on chromatin. Notably, reduced replication is dependent on transcription and the phospho-CTD binding protein CDC73 after depletion of PNUTS/WDR82. Altogether, our results suggest that RNAPII-CTD dephosphorylation is required for the continuous turnover of RNAPII on chromatin, thereby preventing T-R conflicts.

Se alle arbeider i NVA

• Foss, Stian; Bay, Lilli Theres Eilertsen & Andersen, Jan Terje (2026). Design of antibodies for the treatment of Alzheimer's disease. doi: https:/civitan.no/2026/09/19/design-av-antistoffer-for-behandling-av-alzheimers-sykdom/. Fulltekst i vitenarkiv
• Bay, Lilli Theres Eilertsen (2026). TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease. Fulltekst i vitenarkiv
• Bay, Lilli Theres Eilertsen (2026). How does human IgG1 Fc engineering for FcRn mediated half-life extension affects TRIM21 engagement and effector functions? . Fulltekst i vitenarkiv
• Bay, Lilli Theres Eilertsen (2026). How does human IgG1 Fc engineering for FcRn mediated half-life extension affects TRIM21 engagement and effector functions? Fulltekst i vitenarkiv

Se alle arbeider i NVA