scholarly journals p97/VCP- and Lys48-linked polyubiquitination form a new signaling pathway in DNA damage response

Cell Cycle ◽  
2012 ◽  
Vol 11 (6) ◽  
pp. 1062-1069 ◽  
Author(s):  
Kristijan Ramadan
Keyword(s):  
Dna Damage ◽  
Signaling Pathway ◽  
Dna Damage Response ◽  
Damage Response

scholarly journals INTS3 controls the hSSB1-mediated DNA damage response

2009 ◽  
Vol 187 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Jeffrey R. Skaar ◽  
Derek J. Richard ◽  
Anita Saraf ◽  
Alfredo Toschi ◽  
Emma Bolderson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Signaling Pathway ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Binding Protein ◽  
Ataxia Telangiectasia Mutated ◽  
Uncharacterized Protein ◽  
Damage Response ◽  
Atm Signaling Pathway ◽  
Atm Signaling

Human SSB1 (single-stranded binding protein 1 [hSSB1]) was recently identified as a part of the ataxia telangiectasia mutated (ATM) signaling pathway. To investigate hSSB1 function, we performed tandem affinity purifications of hSSB1 mutants mimicking the unphosphorylated and ATM-phosphorylated states. Both hSSB1 mutants copurified a subset of Integrator complex subunits and the uncharacterized protein LOC58493/c9orf80 (henceforth minute INTS3/hSSB-associated element [MISE]). The INTS3–MISE–hSSB1 complex plays a key role in ATM activation and RAD51 recruitment to DNA damage foci during the response to genotoxic stresses. These effects on the DNA damage response are caused by the control of hSSB1 transcription via INTS3, demonstrating a new network controlling hSSB1 function.

scholarly journals Oncogenes and the DNA Damage Response: Myc and E2F1 Engage the ATM Signaling Pathway to Activate p53 and Induce Apoptosis

Cell Cycle ◽  
2006 ◽  
Vol 5 (8) ◽  
pp. 801-803 ◽  
Author(s):  
Sungki Hong ◽  
Raju V. Pusapati ◽  
John T. Powers ◽  
David G. Johnson
Keyword(s):  
Dna Damage ◽  
Signaling Pathway ◽  
Dna Damage Response ◽  
Damage Response ◽  
Atm Signaling Pathway ◽  
Atm Signaling

Crosstalk between Phosphoinositide 3‐kinase/Akt signaling pathway with DNA damage response and oxidative stress in cancer

2018 ◽  
Vol 120 (6) ◽  
pp. 10248-10272 ◽  
Author(s):  
Ansar Karimian ◽  
Sayed Mostafa Mir ◽  
Hadi Parsian ◽  
Sona Refieyan ◽  
Mohammad Mirza‐Aghazadeh‐Attari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Signaling Pathway ◽  
Dna Damage Response ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Damage Response ◽  
Phosphoinositide 3 Kinase ◽  
And Oxidative Stress

scholarly journals BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Li ◽  
Yuantao Wang ◽  
Wanpeng Zhang ◽  
Xinchen Wang ◽  
Lu Chen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Signaling Pathway ◽  
Dna Damage Response ◽  
Triple Negative ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Clinical Indication ◽  
Strand Breaks ◽  
Pi3k Inhibition ◽  
Damage Response

AbstractPoly (ADP-ribose) polymerase (PARP) inhibitors offer a significant clinical benefit for triple-negative breast cancers (TNBCs) with BRCA1/2 mutation. However, the narrow clinical indication limits the development of PARP inhibitors. Phosphoinositide 3-kinase (PI3K) inhibition sensitizes BRCA-proficient TNBC to PARP inhibition, which broadens the indication of PARP inhibitors. Previously researches have reported that PI3K inhibition induced the defect of homologous recombination (HR) mediated repair by downregulating the expression of BRCA1/2 and Rad51. However, the mechanism for their synergistic effects in the treatment of TNBC is still unclear. Herein, we focused on DNA damage, DNA single-strand breaks (SSBs) repair and DNA double-strand breaks (DSBs) repair three aspects to investigate the mechanism of dual PI3K and PARP inhibition in DNA damage response. We found that dual PI3K and PARP inhibition with BKM120 and olaparib significantly reduced the proliferation of BRCA-proficient TNBC cell lines MDA-MB-231 and MDA231-LM2. BKM120 increased cellular ROS to cause DNA oxidative damage. Olaparib resulted in concomitant gain of PARP1, forkhead box M1 (FOXM1) and Exonuclease 1 (Exo1) while inhibited the activity of PARP. BKM120 downregulated the expression of PARP1 and PARP2 to assist olaparib in blocking PARP mediated repair of DNA SSBs. Meanwhile, BKM120 inhibited the expression of BRAC1/2 and Rad51/52 to block HR mediated repair through the PI3K/Akt/NFκB/c-Myc signaling pathway and PI3K/Akt/ FOXM1/Exo1 signaling pathway. BKM120 induced HR deficiency expanded the application of olaparib to HR proficient TNBCs. Our findings proved that PI3K inhibition impaired the repair of both DNA SSBs and DNA DSBs. FOXM1 and Exo1 are novel therapeutic targets that serves important roles in DNA damage response.

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