Downregulation of UBE2E2 in rat liver cells after hepatocarcinogen treatment facilitates cell proliferation and slowing down of DNA damage response in GST-P-expressing preneoplastic lesions

2017 ◽  
Vol 334 ◽  
pp. 207-216 ◽  
Author(s):  
Sayaka Mizukami ◽  
Yousuke Watanabe ◽  
Yukie Saegusa ◽  
Kota Nakajima ◽  
Yuko Ito ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Rat Liver ◽  
Dna Damage Response ◽  
Liver Cells ◽  
Preneoplastic Lesions ◽  
Slowing Down ◽  
Damage Response ◽  
Rat Liver Cells

scholarly journals Hepatotoxic pyrrolizidine alkaloids induce DNA damage response in rat liver in a 28-day feeding study

2020 ◽  
Vol 94 (5) ◽  
pp. 1739-1751 ◽  
Author(s):  
Johanna Ebmeyer ◽  
Josef Daniel Rasinger ◽  
Jan G. Hengstler ◽  
Dirk Schaudien ◽  
Otto Creutzenberg ◽  
...  
Keyword(s):  
Dna Damage ◽  
Rat Liver ◽  
Dna Damage Response ◽  
Pyrrolizidine Alkaloids ◽  
Feeding Study ◽  
Damage Response

scholarly journals Computational correction of off-targeting for CRISPR-Cas9 essentiality screens

2019 ◽  
Author(s):  
Alexendar R. Perez ◽  
Laura Sala ◽  
Richard K. Perez ◽  
Joana A. Vidigal
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Large Scale ◽  
Computational Method ◽  
Seamless Integration ◽  
Guide Rnas ◽  
Cycle Arrest ◽  
Damage Response

Off-target cleavage by Cas9 can confound measurements of cell proliferation/viability in CRISPR assays by eliciting a DNA-damage response that includes cell cycle arrest1-3. This gene-independent toxicity has been documented in large scale assays2-4 and shown to be a source of false-positives when libraries are populated by promiscuous guide RNAs (gRNAs)7. To address this, we developed CSC, a computational method to correct for the effect of specificity on gRNA depletion. We applied CSC to screening data from the Cancer Dependency Map and show that it significantly improves the specificity of CRISPR-Cas9 essentiality screens while preserving known gene essentialities even for genes targeted by highly pro-miscuous guides. We packaged CSC in a Python software to allow its seamless integration into current CRISPR analysis pipelines and improve the sensitivity of essentiality screens for repetitive genomic loci.

scholarly journals Pseudolaric acid B inhibits neuroglioma cell proliferation through DNA damage response

2017 ◽  
Vol 38 (4) ◽  
pp. 2211-2218 ◽  
Author(s):  
Fengmei Song ◽  
Xiaoyan Yu ◽  
Haipeng Zhang ◽  
Zengyan Wang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Pseudolaric Acid B ◽  
Damage Response

The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2996-3004 ◽  
Author(s):  
Maurice Reimann ◽  
Christoph Loddenkemper ◽  
Cornelia Rudolph ◽  
Ines Schildhauer ◽  
Bianca Teichmann ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Treatment Resistance ◽  
Tumor Formation ◽  
Preneoplastic Lesions ◽  
Oncogenic Signaling ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Damage Response

Abstract In addition to the ARF/p53 pathway, the DNA damage response (DDR) has been recognized as another oncogene-provoked anticancer barrier in early human tumorigenesis leading to apoptosis or cellular senescence. DDR mutations may promote tumor formation, but their impact on treatment outcome remains unclear. In this study, we generated ataxia telangiectasia mutated (Atm)–proficient and -deficient B-cell lymphomas in Eμ-myc transgenic mice to examine the role of DDR defects in lymphomagenesis and treatment sensitivity. Atm inactivation accelerated development of lymphomas, and their DNA damage checkpoint defects were virtually indistinguishable from those observed in Atm+/+-derived lymphomas that spontaneously inactivated the proapoptotic Atm/p53 cascade in response to Myc-evoked reactive oxygen species (ROS). Importantly, acquisition of DDR defects, but not selection against the ARF pathway, could be prevented by lifelong exposure to the ROS scavenger N-acetylcysteine (NAC) in vivo. Following anticancer therapy, DDR-compromised lymphomas displayed apoptotic but, surprisingly, no senescence defects and achieved a much poorer long-term outcome when compared with DDR-competent lymphomas treated in vivo. Hence, Atm eliminates preneoplastic lesions by converting oncogenic signaling into apoptosis, and selection against an Atm-dependent response promotes formation of lymphomas with predetermined treatment insensitivity.

scholarly journals The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways

Oncogene ◽  
2009 ◽  
Vol 28 (12) ◽  
pp. 1506-1517 ◽  
Author(s):  
L Mattera ◽  
F Escaffit ◽  
M-J Pillaire ◽  
J Selves ◽  
S Tyteca ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Damage Response

scholarly journals Telomere shortening is correlated with the DNA damage response and telomeric protein down-regulation in colorectal preneoplastic lesions

2008 ◽  
Vol 19 (11) ◽  
pp. 1875-1881 ◽  
Author(s):  
C.M. Raynaud ◽  
S.J. Jang ◽  
P. Nuciforo ◽  
S. Lantuejoul ◽  
E. Brambilla ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Preneoplastic Lesions ◽  
Down Regulation ◽  
Telomere Shortening ◽  
Damage Response ◽  
Telomeric Protein

scholarly journals HSATII RNA is induced via a non-canonical ATM-regulated DNA-damage response pathway and facilitates tumor cell proliferation and movement

2020 ◽  
Author(s):  
Maciej T. Nogalski ◽  
Thomas Shenk
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Rna Expression ◽  
Tumor Cell Proliferation ◽  
Dna Damaging Agents ◽  
Damage Response ◽  
Infected Cells ◽  
Dna Damage Response Pathway

ABSTRACTPericentromeric human satellite II (HSATII) repeats are normally silent, but can be actively transcribed in tumor cells, where increased HSATII copy number is associated with a poor prognosis in colon cancer, and in human cytomegalovirus (HCMV)-infected cells, where the RNA facilitates viral replication. Here, we report that HCMV infection or treatment of ARPE-19 diploid epithelial cells with the DNA-damaging agents, etoposide and zeocin, induced HSATII RNA expression, and a kinase-independent function of ATM was required for the induction. Additionally, various breast cancer cell lines growing in adherent, 2-dimensional cell culture expressed HSATII RNA at different levels, and levels were markedly increased when cells were either infected with HCMV or treated with zeocin. High levels of HSATII RNA expression correlated with enhanced migration of breast cancer cells, and knockdown of HSATII RNA reduced cell migration and the rate of cell proliferation. Our investigation links high expression of HSATII RNA to the DNA damage response, centered on a non-canonical function of ATM, and demonstrates a role for the satellite RNA in tumor cell proliferation and movement.SIGNIFICANCEHSATII RNA is associated with cancer progression, immunostimulation and, as we recently reported, it plays an important role in herpesvirus infections. However, the understanding of cellular processes responsible for the expression of HSATII RNA has been limited. Our current investigation identified a non-canonical, ATM kinase-independent DNA-damage response pathway as a common cellular mechanism regulating HSATII RNA induction in virus-infected cells or cells treated with DNA-damaging agents. Additionally, our study provides a link between expression of HSATII RNA and the cellular growth and migration phenotypes of cancer cells, establishing a new paradigm to study the biological consequences of HSATII RNA expression, i.e., treatment of normal diploid and tumor cells with DNA-damaging agents.

scholarly journals Control of Cell Proliferation, Organ Growth, and DNA Damage Response Operate Independently of Dephosphorylation of the Arabidopsis Cdk1 Homolog CDKA;1

2009 ◽  
Vol 21 (11) ◽  
pp. 3641-3654 ◽  
Author(s):  
Nico Dissmeyer ◽  
Annika K. Weimer ◽  
Stefan Pusch ◽  
Kristof De Schutter ◽  
Claire Lessa Alvim Kamei ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Organ Growth ◽  
Damage Response
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