PRDX1 and MTH1 cooperate to prevent ROS-mediated inhibition of telomerase

Genes & Development
Wareed Ahmed, Joachim Lingner

Abstract

Telomerase counteracts telomere shortening and cellular senescence in germ, stem, and cancer cells by adding repetitive DNA sequences to the ends of chromosomes. Telomeres are susceptible to damage by reactive oxygen species (ROS), but the consequences of oxidation of telomeres on telomere length and the mechanisms that protect from ROS-mediated telomere damage are not well understood. In particular, 8-oxoguanine nucleotides at 3' ends of telomeric substrates inhibit telomerase in vitro, whereas, at internal positions, they suppress G-quadruplex formation and were therefore proposed to promote telomerase activity. Here, we disrupt the peroxiredoxin 1 (PRDX1) and 7,8-dihydro-8-oxoguanine triphosphatase (MTH1) genes in cancer cells and demonstrate that PRDX1 and MTH1 cooperate to prevent accumulation of oxidized guanine in the genome. Concomitant disruption of PRDX1 and MTH1 leads to ROS concentration-dependent continuous shortening of telomeres, which is due to efficient inhibition of telomere extension by telomerase. Our results identify antioxidant systems that are required to protect telomeres from oxidation and are necessary to allow telomere maintenance by telomerase conferring immortality to cancer cells.

References

Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·C G FragaB N Ames
Feb 20, 1997·Nature·B van Steensel, T de Lange
Sep 30, 1999·Nature Medicine·W C HahnR A Weinberg
Feb 3, 2000·Free Radical Biology & Medicine·T von ZglinickiN Sitte
Feb 12, 2000·Molecular and Cellular Biology·A SmogorzewskaT de Lange
Feb 14, 2002·Differentiation; Research in Biological Diversity·Nicholas R ForsythJerry W Shay
Jul 13, 2002·Trends in Biochemical Sciences·Thomas von Zglinicki
Jun 5, 2003·Current Biology : CB·Lorel M ColginRoger R Reddel
Aug 29, 2003·Nature·Mauro SerafiniAlan Crozier
Oct 23, 2003·Aging Cell·Nicholas R ForsythWoodring E Wright
Nov 11, 2003·Nature·Fabrizio d'Adda di FagagnaStephen P Jackson
May 5, 2004·Mutagenesis·Rinne De Bont, Nik van Larebeke
Jun 11, 2004·Nature·Tao LuBruce A Yankner
Jul 21, 2005·The Journal of Biological Chemistry·Patricia L OpreskoVilhelm A Bohr
Jun 22, 2007·Nature·Sheila S DavidSucharita Kundu
Aug 10, 2007·Nature·Eros Lazzerini Denchi, Titia de Lange
Apr 9, 2008·Physiological Reviews·Geraldine Aubert, Peter M Lansdorp
May 30, 2009·Nature Reviews. Drug Discovery·Dunyaporn TrachoothamPeng Huang
Jun 11, 2009·Methods in Molecular Biology·Mizuki OhnoYusaku Nakabeppu
Dec 8, 2009·Science·Titia de Lange
Apr 13, 2011·Current Opinion in Structural Biology·Karl E ZahnSylvie Doublié
Nov 4, 2011·Chromosoma·Angelika L Jacobs, Primo Schär
Feb 24, 2012·Nature Reviews. Molecular Cell Biology·Julian E SaleRoger Woodgate
Jan 26, 2013·Science·Susanne HornRajiv Kumar
Jan 26, 2013·Science·Franklin W HuangLevi A Garraway
Jul 9, 2013·Nature Cell Biology·Foteini MourkiotiHelen M Blau
Aug 22, 2013·Nucleic Acids Research·Morgan E DiolaitiBradley A Stohr
Nov 26, 2013·Nature Communications·Larissa GrolimundJoachim Lingner
Mar 25, 2014·Molecular Cell·Julien SoudetMaria Teresa Teixeira
Aug 16, 2014·Cell Reports·Rhiannon E JonesDuncan M Baird
Oct 25, 2014·Nature Reviews. Cancer·Simran S Sabharwal, Paul T Schumacker
Jun 13, 2015·Genes & Development·Jens C Schmidt, Thomas R Cech
Jun 13, 2015·Trends in Biochemical Sciences·Arden PerkinsP Andrew Karplus
May 12, 2016·Nature Reviews. Molecular Cell Biology·Eros Lazzerini-Denchi, Agnel Sfeir
Nov 8, 2016·Nature Structural & Molecular Biology·Elise FouquerelPatricia L Opresko
Jan 18, 2017·Nature Reviews. Molecular Cell Biology·John Maciejowski, Titia de Lange
Oct 6, 2017·Nucleic Acids Research·Hui-Ting LeeSua Myong
Dec 25, 2017·Differentiation; Research in Biological Diversity·Wareed Ahmed, Joachim Lingner

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Citations

Jul 16, 2019·Yeast·Zhou Xu, Maria Teresa Teixeira
Nov 30, 2018·Antioxidants·James D WestMatthew A Loberg
Apr 8, 2020·International Journal of Molecular Sciences·Pavel VodickaLudmila Vodickova
Jan 6, 2019·Antioxidants·Tom E ForshawCristina M Furdui
May 29, 2018·Genes & Development·Susan Smith
Apr 2, 2020·Nature Reviews. Molecular Cell Biology·Helmut Sies, Dean P Jones
Oct 11, 2019·International Journal of Molecular Sciences·Pauline Billard, Delphine A Poncet
Oct 22, 2020·Nature Communications·Samantha L SanfordPatricia L Opresko
May 8, 2020·Mechanisms of Ageing and Development·Maria Sol Jacome Burbano, Eric Gilson
Sep 11, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·José Santiago Ibáñez-CabellosFederico V Pallardó
Nov 3, 2020·Frontiers in Psychiatry·Martin LundbergMartin Schalling
Jun 3, 2021·Cells·Maria Sol Jacome Burbano, Eric Gilson
Jul 17, 2021·European Archives of Psychiatry and Clinical Neuroscience·Karen M RyanDeclan M McLoughlin
Jul 14, 2021·Proceedings of the National Academy of Sciences of the United States of America·Deepavali ChakravartiRonald A DePinho
Jun 13, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chaoliang TangXiaoqing Chai
Aug 10, 2021·DNA Repair·Samantha L SanfordPatricia L Opresko
Aug 24, 2021·Frontiers in Cell and Developmental Biology·Sergey A SinenkoAlexey N Tomilin
Nov 27, 2021·Molecular Ecology·Martin ReichardMiguel Godinho Ferreira

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