scholarly journals ATM and ATR Pathways Signal Alternative Splicing of Drosophila TAF1 Pre-mRNA in Response to DNA Damage

2006 ◽  
Vol 26 (24) ◽  
pp. 9256-9267 ◽  
Author(s):  
Rebeccah J. Katzenberger ◽  
Matthew S. Marengo ◽  
David A. Wassarman
Keyword(s):  
Dna Damage ◽  
Alternative Splicing ◽  
Ionizing Radiation ◽  
Rna Polymerase Ii ◽  
Protein Coding ◽  
Major Mechanism ◽  
Radiation Induced ◽  
A Subunit ◽  
Eukaryotic Organisms

ABSTRACT Alternative pre-mRNA splicing is a major mechanism utilized by eukaryotic organisms to expand their protein-coding capacity. To examine the role of cell signaling in regulating alternative splicing, we analyzed the splicing of the Drosophila melanogaster TAF1 pre-mRNA. TAF1 encodes a subunit of TFIID, which is broadly required for RNA polymerase II transcription. We demonstrate that TAF1 alternative splicing generates four mRNAs, TAF1-1, TAF1-2, TAF1-3, and TAF1-4, of which TAF1-2 and TAF1-4 encode proteins that directly bind DNA through AT hooks. TAF1 alternative splicing was regulated in a tissue-specific manner and in response to DNA damage induced by ionizing radiation or camptothecin. Pharmacological inhibitors and RNA interference were used to demonstrate that ionizing-radiation-induced upregulation of TAF1-3 and TAF1-4 splicing in S2 cells was mediated by the ATM (ataxia-telangiectasia mutated) DNA damage response kinase and checkpoint kinase 2 (CHK2), a known ATM substrate. Similarly, camptothecin-induced upregulation of TAF1-3 and TAF1-4 splicing was mediated by ATR (ATM-RAD3 related) and CHK1. These findings suggest that inducible TAF1 alternative splicing is a mechanism to regulate transcription in response to developmental or DNA damage signals and provide the first evidence that the ATM/CHK2 and ATR/CHK1 signaling pathways control gene expression by regulating alternative splicing.

scholarly journals Role of Ferulic Acid in the Amelioration of Ionizing Radiation Induced Inflammation: A Murine Model

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e97599 ◽  
Author(s):  
Ujjal Das ◽  
Krishnendu Manna ◽  
Mahuya Sinha ◽  
Sanjukta Datta ◽  
Dipesh Kr Das ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Ferulic Acid ◽  
Murine Model ◽  
Radiation Induced

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 Arabidopsis Mediator subunit 17 connects transcription with DNA repair after UV-B exposure

2021 ◽  
Author(s):  
Marisol Giustozzi ◽  
Santiago Freytes ◽  
Aime Jaskolowski ◽  
Micaela Lichy ◽  
Julieta L. Mateos ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Transcription Initiation ◽  
Plant Responses ◽  
Repair System ◽  
Root Tips ◽  
Direct Role ◽  
Altered Expression ◽  
Eukaryotic Organisms

Mediator 17 (MED17) is a subunit of the Mediator complex that regulates transcription initiation in eukaryotic organisms. In yeast and humans, MED17 also participates in DNA repair, physically interacting with proteins of the Nucleotide Excision DNA Repair system. We here analyzed the role of MED17 in Arabidopsis plants exposed to UV-B radiation, which role has not been previously described. Comparison of med17 mutant transcriptome to that of WT plants showed that almost one third of transcripts with altered expression in med17 plants are also changed by UV-B exposure in WT plants. To validate the role of MED17 in UV-B irradiated plants, plant responses to UV-B were analyzed, including flowering time, DNA damage accumulation and programmed cell death in the meristematic cells of the root tips. Our results show that med17 and OE MED17 plants have altered responses to UV-B; and that MED17 participates in various aspects of the DNA damage response (DDR). Increased sensitivity to DDR after UV-B in med17 plants can be due to altered regulation of UV-B responsive transcripts; but additionally MED17 physically interacts with DNA repair proteins, suggesting a direct role of this Mediator subunit during repair. Finally, we here also show that MED17 is necessary to regulate the DDR activated by ATR, and that PDCD5 overexpression reverts the deficiencies in DDR shown in med17 mutants. Together, the data presented demonstrates that MED17 is an important regulator of the DDR after UV-B radiation in Arabidopsis plants.

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.

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