URI is required to maintain intestinal architecture during ionizing radiation

Science ◽  
2019 ◽  
Vol 364 (6443) ◽  
pp. eaaq1165 ◽  
Author(s):  
Almudena Chaves-Pérez ◽  
Mahmut Yilmaz ◽  
Cristian Perna ◽  
Sergio de la Rosa ◽  
Nabil Djouder
Keyword(s):  
At Risk ◽  
Dna Damage ◽  
Stem Cell ◽  
Ionizing Radiation ◽  
Tissue Regeneration ◽  
High Dose ◽  
Intestinal Crypt ◽  
Dose Irradiation ◽  
Organ Regeneration ◽  
Radiation Induced

Ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a lethal disorder, by means of unknown mechanisms. We show that high-dose irradiation increases unconventional prefoldin RPB5 interactor (URI) levels in mouse intestinal crypt, but organ regeneration correlates with URI reductions. URI overexpression in intestine protects mice from radiation-induced GIS, whereas halving URI expression sensitizes mice to IR. URI specifically inhibits β-catenin in stem cell–like label-retaining (LR) cells, which are essential for organ regeneration after IR. URI reduction activates β-catenin–induced c-MYC expression, causing proliferation of and DNA damage to LR cells, rendering them radiosensitive. Therefore, URI labels LR cells which promote tissue regeneration in response to high-dose irradiation, and c-MYC inhibitors could be countermeasures for humans at risk of developing GIS.

scholarly journals Truncated PPM1D Prevents Apoptosis in the Murine Thymus and Promotes Ionizing Radiation-Induced Lymphoma

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2068
Author(s):  
Andra S. Martinikova ◽  
Monika Burocziova ◽  
Miroslav Stoyanov ◽  
Libor Macurek
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Tumor Formation ◽  
Cell Cycle Checkpoints ◽  
Negative Regulator ◽  
Tumor Suppressor P53 ◽  
Mouse Thymus ◽  
Truncating Mutation ◽  
T Cell Lymphomas ◽  
Radiation Induced

Genome integrity is protected by the cell-cycle checkpoints that prevent cell proliferation in the presence of DNA damage and allow time for DNA repair. The transient checkpoint arrest together with cellular senescence represent an intrinsic barrier to tumorigenesis. Tumor suppressor p53 is an integral part of the checkpoints and its inactivating mutations promote cancer growth. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of p53. Although its loss impairs recovery from the G2 checkpoint and promotes induction of senescence, amplification of the PPM1D locus or gain-of-function truncating mutations of PPM1D occur in various cancers. Here we used a transgenic mouse model carrying a truncating mutation in exon 6 of PPM1D (Ppm1dT). As with human cell lines, we found that the truncated PPM1D was present at high levels in the mouse thymus. Truncated PPM1D did not affect differentiation of T-cells in the thymus but it impaired their response to ionizing radiation (IR). Thymocytes in Ppm1dT/+ mice did not arrest in the checkpoint and continued to proliferate despite the presence of DNA damage. In addition, we observed a decreased level of apoptosis in the thymi of Ppm1dT/+ mice. Moreover, the frequency of the IR-induced T-cell lymphomas increased in Ppm1dT/+Trp53+/− mice resulting in decreased survival. We conclude that truncated PPM1D partially suppresses the p53 pathway in the mouse thymus and potentiates tumor formation under the condition of a partial loss of p53 function.

scholarly journals Restoration of DNA Integrity and Cell Cycle by Electric Stimulation in Planarian Tissues Damaged by Ionizing Radiation

2021 ◽  
Author(s):  
Devon Davidian ◽  
Melanie LeGro ◽  
Paul Barghouth ◽  
Salvador Rojas ◽  
Benjamin Ziman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Ionizing Radiation ◽  
Electric Stimulation ◽  
Ectopic Expression ◽  
Cell Activity ◽  
Pharmacological Intervention ◽  
Dna Integrity ◽  
High Dose ◽  
Stem Cell Markers

Exposure to high levels of ionizing y-radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity to reestablish stem cell activity in tissues damaged by ionizing radiation. We show that sub-threshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally y-irradiated tissues of the planarian flatworm Schmidtea mediterranea. Our findings reveal that DCS enhances DNA repair, transcriptional activity, and cell cycle entry in post-mitotic cells. These responses involve rapid increases in cytosolic [Ca2+] through the activation of L-type Cav channels and intracellular Ca2+ stores leading to the activation of immediate early genes and ectopic expression of stem cell markers in postmitotic cells. Overall, we show the potential of electric current stimulation to reverse damaging effects of high dose y-radiation in adult tissues. Furthermore, our results provide mechanistic insights describing how electric stimulation effectively translates into molecular responses capable of regulating fundamental cellular functions without the need for genetic or pharmacological intervention.

Irreversible electron attachment – a key to DNA damage by solvated electrons in aqueous solution

2015 ◽  
Vol 13 (41) ◽  
pp. 10362-10369 ◽  
Author(s):  
K. Westphal ◽  
J. Wiczk ◽  
J. Miloch ◽  
G. Kciuk ◽  
K. Bobrowski ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Electron Attachment ◽  
Solvated Electrons ◽  
Radiation Induced

In an aqueous solution trinucleotides labeled with bromonucleobases are damaged by ionizing radiation induced electrons while native trimers are insensitive to electrons under the same conditions.

Analysis of ionizing radiation-induced foci of DNA damage repair proteins

2005 ◽  
Vol 574 (1-2) ◽  
pp. 22-33 ◽  
Author(s):  
Lieneke R. van Veelen ◽  
Tiziana Cervelli ◽  
Mandy W.M.M. van de Rakt ◽  
Arjan F. Theil ◽  
Jeroen Essers ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Radiation Induced

Luminescence and radiation-induced color centers in anion-defective alumina crystals after high-dose irradiation

2016 ◽  
Vol 90 ◽  
pp. 90-93 ◽  
Author(s):  
V.S. Kortov ◽  
V.A. Pustovarov ◽  
S.V. Zvonarev ◽  
T.V. Shtang
Keyword(s):  
Color Centers ◽  
High Dose ◽  
Dose Irradiation ◽  
Radiation Induced
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