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Genotoxic Stress

MedGen UID:
222489
•Concept ID:
C1257899
•
Cell or Molecular Dysfunction
Synonyms: Genotoxic Stresses; Stress, Genotoxic; Stresses, Genotoxic

Definition

Exposure to DNA-damaging agents and subsequent energy expenditures by a cell to repair DNA damage. Genotoxic stress elicits biochemical responses that either enhance cell survival or lead to cell death. These biochemical responses include DNA-damage-inducible repair and increasing expression of a variety of proteins by both transcriptional and post-transcriptional mechanisms. Genotoxic stresses frequently activate signal transduction pathways that originate in the cell membrane or cytoplasm, triggering similar phosphorylation cascades to those induced by the activation of cell-surface receptors. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGenotoxic Stress

Professional guidelines

PubMed

Stress management by autophagy: Implications for chemoresistance.
Huang Z, Zhou L, Chen Z, Nice EC, Huang C
Int J Cancer 2016 Jul 1;139(1):23-32. Epub 2016 Jan 28 doi: 10.1002/ijc.29990. PMID: 26757106
Modulation of cellular response to anticancer treatment by caffeine: inhibition of cell cycle checkpoints, DNA repair and more.
Sabisz M, Skladanowski A
Curr Pharm Biotechnol 2008 Aug;9(4):325-36. doi: 10.2174/138920108785161497. PMID: 18691092
Genetic toxicity assessment: employing the best science for human safety evaluation Part VII: Why not start with a single test: a transformational alternative to genotoxicity hazard and risk assessment.
Ku WW, Aubrecht J, Mauthe RJ, Schiestl RH, Fornace AJ Jr
Toxicol Sci 2007 Sep;99(1):20-5. Epub 2007 Jun 4 doi: 10.1093/toxsci/kfm147. PMID: 17548889

Recent clinical studies

Etiology

DNA damage-how and why we age?
Yousefzadeh M, Henpita C, Vyas R, Soto-Palma C, Robbins P, Niedernhofer L
Elife 2021 Jan 29;10 doi: 10.7554/eLife.62852. PMID: 33512317Free PMC Article
Clonal hematopoiesis in cancer.
Park SJ, Bejar R
Exp Hematol 2020 Mar;83:105-112. Epub 2020 Feb 7 doi: 10.1016/j.exphem.2020.02.001. PMID: 32044376Free PMC Article
ROS and the DNA damage response in cancer.
Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD
Redox Biol 2019 Jul;25:101084. Epub 2018 Dec 21 doi: 10.1016/j.redox.2018.101084. PMID: 30612957Free PMC Article
Genotoxic Stress-Induced Senescence.
Fan DNY, Schmitt CA
Methods Mol Biol 2019;1896:93-105. doi: 10.1007/978-1-4939-8931-7_10. PMID: 30474843
Fisetin is a senotherapeutic that extends health and lifespan.
Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ
EBioMedicine 2018 Oct;36:18-28. Epub 2018 Sep 29 doi: 10.1016/j.ebiom.2018.09.015. PMID: 30279143Free PMC Article

Diagnosis

Functions of Thrombospondin-1 in the Tumor Microenvironment.
Kaur S, Bronson SM, Pal-Nath D, Miller TW, Soto-Pantoja DR, Roberts DD
Int J Mol Sci 2021 Apr 27;22(9) doi: 10.3390/ijms22094570. PMID: 33925464Free PMC Article
Cellular senescence in cancer: from mechanisms to detection.
Ou HL, Hoffmann R, González-López C, Doherty GJ, Korkola JE, Muñoz-Espín D
Mol Oncol 2021 Oct;15(10):2634-2671. Epub 2020 Oct 22 doi: 10.1002/1878-0261.12807. PMID: 32981205Free PMC Article
Genotoxic Stress-Induced Senescence.
Fan DNY, Schmitt CA
Methods Mol Biol 2019;1896:93-105. doi: 10.1007/978-1-4939-8931-7_10. PMID: 30474843
Ataxia telangiectasia: a review.
Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM
Orphanet J Rare Dis 2016 Nov 25;11(1):159. doi: 10.1186/s13023-016-0543-7. PMID: 27884168Free PMC Article
p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents.
Sui X, Kong N, Ye L, Han W, Zhou J, Zhang Q, He C, Pan H
Cancer Lett 2014 Mar 28;344(2):174-9. Epub 2013 Dec 11 doi: 10.1016/j.canlet.2013.11.019. PMID: 24333738

Therapy

Targeting Apoptosis in Cancer.
Singh P, Lim B
Curr Oncol Rep 2022 Mar;24(3):273-284. Epub 2022 Feb 3 doi: 10.1007/s11912-022-01199-y. PMID: 35113355
Fisetin is a senotherapeutic that extends health and lifespan.
Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ
EBioMedicine 2018 Oct;36:18-28. Epub 2018 Sep 29 doi: 10.1016/j.ebiom.2018.09.015. PMID: 30279143Free PMC Article
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response.
Blackford AN, Jackson SP
Mol Cell 2017 Jun 15;66(6):801-817. doi: 10.1016/j.molcel.2017.05.015. PMID: 28622525
Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies.
Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D'Orazi G
Aging (Albany NY) 2016 Apr;8(4):603-19. doi: 10.18632/aging.100934. PMID: 27019364Free PMC Article
Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor.
Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J
PLoS Biol 2008 Dec 2;6(12):2853-68. doi: 10.1371/journal.pbio.0060301. PMID: 19053174Free PMC Article

Prognosis

Role of p53 in breast cancer progression: An insight into p53 targeted therapy.
Marvalim C, Datta A, Lee SC
Theranostics 2023;13(4):1421-1442. Epub 2023 Feb 27 doi: 10.7150/thno.81847. PMID: 36923534Free PMC Article
KDM6 demethylases integrate DNA repair gene regulation and loss of KDM6A sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition.
Boila LD, Ghosh S, Bandyopadhyay SK, Jin L, Murison A, Zeng AGX, Shaikh W, Bhowmik S, Muddineni SSNA, Biswas M, Sinha S, Chatterjee SS, Mbong N, Gan OI, Bose A, Chakraborty S, Arruda A, Kennedy JA, Mitchell A, Lechman ER, Banerjee D, Milyavsky M, Minden MD, Dick JE, Sengupta A
Leukemia 2023 Apr;37(4):751-764. Epub 2023 Jan 31 doi: 10.1038/s41375-023-01833-z. PMID: 36720973
CDK4/6 inhibitors induce replication stress to cause long-term cell cycle withdrawal.
Crozier L, Foy R, Mouery BL, Whitaker RH, Corno A, Spanos C, Ly T, Gowen Cook J, Saurin AT
EMBO J 2022 Mar 15;41(6):e108599. Epub 2022 Jan 17 doi: 10.15252/embj.2021108599. PMID: 35037284Free PMC Article
Epigenetic regulation of DNA repair genes and implications for tumor therapy.
Christmann M, Kaina B
Mutat Res Rev Mutat Res 2019 Apr-Jun;780:15-28. Epub 2017 Oct 7 doi: 10.1016/j.mrrev.2017.10.001. PMID: 31395346
Ataxia telangiectasia: a review.
Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM
Orphanet J Rare Dis 2016 Nov 25;11(1):159. doi: 10.1186/s13023-016-0543-7. PMID: 27884168Free PMC Article

Clinical prediction guides

Pathological consequences of DNA damage in the kidney.
Garaycoechea JI, Quinlan C, Luijsterburg MS
Nat Rev Nephrol 2023 Apr;19(4):229-243. Epub 2023 Jan 26 doi: 10.1038/s41581-022-00671-z. PMID: 36702905
CDK4/6 inhibitors induce replication stress to cause long-term cell cycle withdrawal.
Crozier L, Foy R, Mouery BL, Whitaker RH, Corno A, Spanos C, Ly T, Gowen Cook J, Saurin AT
EMBO J 2022 Mar 15;41(6):e108599. Epub 2022 Jan 17 doi: 10.15252/embj.2021108599. PMID: 35037284Free PMC Article
p53 mRNA Metabolism Links with the DNA Damage Response.
Vadivel Gnanasundram S, Bonczek O, Wang L, Chen S, Fahraeus R
Genes (Basel) 2021 Sep 20;12(9) doi: 10.3390/genes12091446. PMID: 34573428Free PMC Article
Clonal hematopoiesis and risk for hematologic malignancy.
Warren JT, Link DC
Blood 2020 Oct 1;136(14):1599-1605. doi: 10.1182/blood.2019000991. PMID: 32736382Free PMC Article
BIRC5/Survivin is a novel ATG12-ATG5 conjugate interactor and an autophagy-induced DNA damage suppressor in human cancer and mouse embryonic fibroblast cells.
Lin TY, Chan HH, Chen SH, Sarvagalla S, Chen PS, Coumar MS, Cheng SM, Chang YC, Lin CH, Leung E, Cheung CHA
Autophagy 2020 Jul;16(7):1296-1313. Epub 2019 Oct 15 doi: 10.1080/15548627.2019.1671643. PMID: 31612776Free PMC Article

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