PB01 Suppresses Radio-Resistance by Regulating ATR Signaling in Human Non-Small-Cell Lung Cancer Cells

Scientists reported the antitumor effects and mechanism of a novel benzothiazole derivative 4-methoxy-cyclohexane carboxylic acid [2-(3,5-dimethyl-isoxazole-4-yl) sulpanil-benzothiazole-6-yl]-amide (PB01) in radiation-resistant human non-small-cell lung cancer cells.
[Scientific Reports]
Kim, T. W., Hong, D.-W., & Hong, S. H. (2021). PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells. Scientific Reports, 11(1), 12093. https://doi.org/10.1038/s41598-021-91716-z Cite
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GATA3 Induces Mitochondrial Biogenesis in Primary Human CD4+ T Cells during DNA Damage

Investigators showed a mechanism utilised by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK.
[Nature Communications]
Callender, L. A., Schroth, J., Carroll, E. C., Garrod-Ketchley, C., Romano, L. E. L., Hendy, E., Kelly, A., Lavender, P., Akbar, A. N., Chapple, J. P., & Henson, S. M. (2021). GATA3 induces mitochondrial biogenesis in primary human CD4+ T cells during DNA damage. Nature Communications, 12(1), 3379. https://doi.org/10.1038/s41467-021-23715-7 Cite
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Selenomethionine Protects Hematopoietic Stem/Progenitor Cells against Cobalt Nanoparticles by Stimulating Antioxidant Actions and DNA Repair Functions

The authors investigated the mechanism underlying the toxic effect of cobalt nanoparticles (CoNPs) on HSCs/hematopoietic progenitor cells and to determine the protective effect of selenomethionine against CoNPs in vitro and in vivo.
[Aging]
Zhu, W., Liu, Y., Zhang, W., Fan, W., Wang, S., Gu, J.-H., Sun, H., & Liu, F. (2021). Selenomethionine protects hematopoietic stem/progenitor cells against cobalt nanoparticles by stimulating antioxidant actions and DNA repair functions. Aging, 13. https://doi.org/10.18632/aging.202865 Cite
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SLFN11 Inactivation Induces Proteotoxic Stress and Sensitizes Cancer Cells to Ubiquitin Activating Enzyme Inhibitor TAK-243

Researchers report that TAK-243, a first-in-class ubiquitin activating enzyme UBA1 inhibitor in clinical development, caused preferential cytotoxicity in SLFN11-knock out cells.
[Cancer Research]
Murai, Y., Jo, U., Murai, J., Jenkins, L., Huang, S.-Y. N., Chakka, S., Chen, L., Cheng, K., Fukuda, S., Takebe, N., & Pommier, Y. (2021). SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-2694 Cite
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Therapeutic Targeting of ATR Yields Durable Regressions in Small Cell Lung Cancers with High Replication Stress

Using chemical genetic screens, scientists identified inhibition of ataxia telangiectasia and rad3 related (ATR), the primary activator of the replication stress response, and topoisomerase I (TOP1), nuclear enzyme that suppressed genomic instability, as synergistically cytotoxic in small cell lung cancer (SCLC).
[Cancer Cell]
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Loss of the Abasic Site Sensor HMCES Is Synthetic Lethal with the Activity of the APOBEC3A Cytosine Deaminase in Cancer Cells

The authors report the implementation of CRISPR/Cas-9 genetic screening to identify susceptibilities of multiple A3A-expressing lung adenocarcinoma cell lines.
[PLoS Biology]
Biayna, J., Garcia-Cao, I., Álvarez, M. M., Salvadores, M., Espinosa-Carrasco, J., McCullough, M., Supek, F., & Stracker, T. H. (2021). Loss of the abasic site sensor HMCES is synthetic lethal with the activity of the APOBEC3A cytosine deaminase in cancer cells. PLOS Biology, 19(3), e3001176. https://doi.org/10.1371/journal.pbio.3001176 Cite
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MYBL2 and ATM Suppress Replication Stress in Pluripotent Stem Cells

The authors proposed that in addition to ataxia‐telangiectasia and Rad3 related (ATR), a MYBL2‐MRN‐ATM replication stress response pathway functioned in ESCs to control DNA replication initiation and prevent genome instability.
[EMBO Reports]
Blakemore, D., Vilaplana-Lopera, N., Almaghrabi, R., Gonzalez, E., Moya, M., Ward, C., Murphy, G., Gambus, A., Petermann, E., Stewart, G. S., & García, P. (2021). MYBL2 and ATM suppress replication stress in pluripotent stem cells. EMBO Reports, n/a(n/a), e51120. https://doi.org/10.15252/embr.202051120 Cite
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Ddx41 Inhibition of DNA Damage Signaling Permits Erythroid Progenitor Expansion in Zebrafish

Researchers demonstrated that loss of DEAD-box Helicase 41 (ddx41) led to anemia caused by diminished proliferation and defective differentiation of erythroid progenitors.
[Haematologica]
Weinreb, J. T., Gupta, V., Sharvit, E., Weil, R., & Bowman, T. V. (2020). Ddx41 inhibition of DNA damage signaling permits erythroid progenitor expansion in zebrafish. Haematologica. https://doi.org/10.3324/haematol.2020.257246 Cite
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Antiviral Drug Screen Identifies DNA-Damage Response Inhibitor as Potent Blocker of SARS-CoV-2 Replication

Scientists developed a medium-throughput drug screening system and identified a small molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting SARS-CoV-2 cytopathic effect in human epithelial cells.
[Cell Reports]
Garcia, G., Sharma, A., Ramaiah, A., Sen, C., Purkayastha, A., Kohn, D. B., Parcells, M. S., Beck, S., Kim, H., Bakowski, M. A., Kirkpatrick, M. G., Riva, L., Wolff, K. C., Han, B., Yuen, C., Ulmert, D., Purbey, P. K., Scumpia, P., Beutler, N., … Arumugaswami, V. (2021). Antiviral Drug Screen Identifies DNA-Damage Response Inhibitor as Potent Blocker of SARS-CoV-2 Replication. Cell Reports, 0(0). https://doi.org/10.1016/j.celrep.2021.108940 Cite
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Control of Replication Stress and Mitosis in Colorectal Cancer Stem Cells through the Interplay of PARP1, MRE11 and RAD51

Researchers showed that the replication stress response was efficient in primary CSCs from colorectal cancer, and described unique roles for PARP1 and MRE11/RAD51.
[Cell Death & Differentiation]
Manic, G., Musella, M., Corradi, F., Sistigu, A., Vitale, S., Soliman Abdel Rehim, S., Mattiello, L., Malacaria, E., Galassi, C., Signore, M., Pallocca, M., Scalera, S., Goeman, F., De Nicola, F., Guarracino, A., Pennisi, R., Antonangeli, F., Sperati, F., Baiocchi, M., … Vitale, I. (2021). Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51. Cell Death & Differentiation, 1–23. https://doi.org/10.1038/s41418-020-00733-4 Cite
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DNA Damage in Human Glomerular Endothelial Cells Induces Nodular Glomerulosclerosis via an ATR and ANXA2 Pathway

In in vitro studies, collagen type VI secretion from human renal glomerular endothelial cells was assessed by measuring the decrease in the cytoplasmic COL6-positive cells and an increase in the amount of COL6 in the culture medium.
[Scientific Reports]
Fujii, A., Sunatani, Y., Furuichi, K., Fujimoto, K., Adachi, H., Iwabuchi, K., & Yokoyama, H. (2020). DNA damage in human glomerular endothelial cells induces nodular glomerulosclerosis via an ATR and ANXA2 pathway. Scientific Reports, 10(1), 22206. https://doi.org/10.1038/s41598-020-79106-3 Cite
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