scholarly journals Notch is a direct negative regulator of the DNA-damage response

2015 ◽  
Vol 22 (5) ◽  
pp. 417-424 ◽  
Author(s):  
Jelena Vermezovic ◽  
Marek Adamowicz ◽  
Libero Santarpia ◽  
Alessandra Rustighi ◽  
Mattia Forcato ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Negative Regulator ◽  
Damage Response

scholarly journals Interplay between Mdm2 and HIPK2 in the DNA damage response

2014 ◽  
Vol 11 (96) ◽  
pp. 20140319 ◽  
Author(s):  
Xiao-Peng Zhang ◽  
Feng Liu ◽  
Wei Wang
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Negative Regulator ◽  
Critical Event ◽  
Apoptosis Induction ◽  
Nuclear Entry ◽  
Induce Cell Cycle Arrest ◽  
Interacting Protein ◽  
Cycle Arrest ◽  
Damage Response

The tumour suppressor p53 is activated to induce cell-cycle arrest or apoptosis in the DNA damage response (DDR). p53 phosphorylation at Ser46 by HIPK2 (homeodomain-interacting protein kinase 2) is a critical event in apoptosis induction. Interestingly, HIPK2 is degraded by Mdm2 (a negative regulator of p53), whereas Mdm2 is downregulated by HIPK2 through several mechanisms. Here, we develop a four-module network model for the p53 pathway to clarify the role of interplay between Mdm2 and HIPK2 in the DDR evoked by ultraviolet radiation. By numerical simulations, we reveal that Mdm2-dependent HIPK2 degradation promotes cell survival after mild DNA damage and that inhibition of HIPK2 degradation is sufficient to trigger apoptosis. In response to severe damage, p53 phosphorylation at Ser46 is promoted by the accumulation of HIPK2 due to downregulation of nuclear Mdm2 in the later phase of the response. Meanwhile, the concentration of p53 switches from moderate to high levels, contributing to apoptosis induction. We show that the presence of three mechanisms for Mdm2 downregulation, i.e. repression of mdm2 expression, inhibition of its nuclear entry and HIPK2-induced degradation, guarantees the apoptosis of irreparably damaged cells. Our results agree well with multiple experimental observations, and testable predictions are also made. This work advances our understanding of the regulation of p53 activity in the DDR and suggests that HIPK2 should be a significant target for cancer therapy.

scholarly journals XAP5 CIRCADIAN TIMEKEEPER Affects Both DNA Damage Responses and Immune Signaling in Arabidopsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Roderick W. Kumimoto ◽  
Cory T. Ellison ◽  
Tania Y. Toruño ◽  
Aurélie Bak ◽  
Hongtao Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Pseudomonas Syringae ◽  
Dna Damage Response ◽  
Elevated Temperatures ◽  
Bacterial Pathogen ◽  
Negative Regulator ◽  
Positive Role ◽  
Damage Repair ◽  
Damage Response ◽  
Effector Triggered Immunity

Numerous links have been reported between immune response and DNA damage repair pathways in both plants and animals but the precise nature of the relationship between these fundamental processes is not entirely clear. Here, we report that XAP5 CIRCADIAN TIMEKEEPER (XCT), a protein highly conserved across eukaryotes, acts as a negative regulator of immunity in Arabidopsis thaliana and plays a positive role in responses to DNA damaging radiation. We find xct mutants have enhanced resistance to infection by a virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000, and are hyper-responsive to the defense-activating hormone salicylic acid (SA) when compared to wild-type. Unlike most mutants with constitutive effector-triggered immunity (ETI), xct plants do not have increased levels of SA and retain enhanced immunity at elevated temperatures. Genetic analysis indicates XCT acts independently of NONEXPRESSOR OF PATHOGENESIS RELATED GENES1 (NPR1), which encodes a known SA receptor. Since DNA damage has been reported to potentiate immune responses, we next investigated the DNA damage response in our mutants. We found xct seedlings to be hypersensitive to UV-C and γ radiation and deficient in phosphorylation of the histone variant H2A.X, one of the earliest known responses to DNA damage. These data demonstrate that loss of XCT causes a defect in an early step of the DNA damage response pathway. Together, our data suggest that alterations in DNA damage response pathways may underlie the enhanced immunity seen in xct mutants.

2118-P: Regulation of Ataxia-Telangiectasia and Rad3-Related (ATR)–Dependent DNA Damage Response by Nitric Oxide in ß-Cells

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2118-P
Author(s):  
CHAY TENG YEO ◽  
BRYNDON OLESON ◽  
JOHN A. CORBETT ◽  
JAMIE K. SCHNUCK
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Damage Response

DNA damage response and neuroprotection

10.2741/2862 ◽  
2008 ◽  
Vol 13 (13) ◽  
pp. 2504 ◽  
Author(s):  
Inna, I. Kruman
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response
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