TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage

Cell
Jing YeEric Gilson

Abstract

Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2 regulates the 5' exonuclease activity of its binding partner, Apollo, a member of the metallo-beta-lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome ends. Genetic data indicate that DNA topoisomerase 2alpha acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1, TOP2alpha, and TOP2beta at telomeres. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres.

References

Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M M HeckW C Earnshaw
Apr 20, 1986·Journal of Molecular Biology·S M GasserU K Laemmli
Nov 5, 1997·Nature Genetics·D BroccoliT de Lange
Nov 5, 1997·Nature Genetics·T BilaudE Gilson
Feb 26, 1998·Cell·B van SteenselT de Lange
May 25, 1999·Cell·J D GriffithT de Lange
Nov 27, 1999·Cytogenetics and Cell Genetics·C DesmazeL Sabatier
Feb 12, 2000·Molecular and Cellular Biology·A SmogorzewskaT de Lange
Jul 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·L PostowN R Cozzarelli
Sep 27, 2001·Cell·E H Blackburn
Sep 28, 2001·The EMBO Journal·R M StanselJ D Griffith
Apr 9, 2002·European Journal of Human Genetics : EJHG·Cécile Mignon-RavixMarie-Geneviève Mattei
Sep 6, 2003·Current Biology : CB·Hiroyuki TakaiTitia de Lange
Nov 11, 2003·Nature·Fabrizio d'Adda di FagagnaStephen P Jackson
Jan 28, 2004·The Journal of Experimental Medicine·Catherine PoinsignonJean-Pierre de Villartay
Apr 9, 2004·The EMBO Journal·Ulrich PannickeKlaus Schwarz
Jun 1, 2004·Molecular and Cellular Biology·Karin A MatternJ Mark J M Zijlmans
Jun 22, 2005·Nature Cell Biology·Giulia B Celli, Titia de Lange
Dec 13, 2005·Cancer Cell·Marc DamelinTimothy H Bestor
Apr 7, 2006·Nature·Kyle M MillerJulia Promisel Cooper
Apr 12, 2006·The Journal of Biological Chemistry·Brian D Freibaum, Christopher M Counter
May 30, 2006·Current Biology : CB·Christelle LenainEric Gilson
May 30, 2006·Current Biology : CB·Megan van Overbeek, Titia de Lange
Sep 27, 2006·Molecular Microbiology·Troy BankheadGeorge Chaconas
Jan 16, 2007·Nature Structural & Molecular Biology·Simon AmiardMarie-Josèphe Giraud-Panis
Mar 24, 2007·DNA Repair·Hélène Tourrière, Philippe Pasero
Jun 5, 2007·Nature Protocols·Michael Fenech
Sep 7, 2007·Nucleic Acids Research·James HejnaRobb Moses
Sep 22, 2007·Nature Reviews. Molecular Cell Biology·Eric Gilson, Vincent Géli
Oct 13, 2007·The Journal of Clinical Investigation·Erica SalvatiAnnamaria Biroccio
Aug 6, 2008·Annual Review of Genetics·Wilhelm Palm, Titia de Lange
Feb 14, 2009·PLoS Genetics·Jean-Baptiste VannierMaria Eugenia Gallego
Apr 21, 2009·Nature Reviews. Cancer·John L Nitiss
Jun 2, 2009·DNA Repair·Dana Branzei, Marco Foiani
Aug 15, 2009·The EMBO Journal·Thomas GermeJulia Promisel Cooper
Oct 30, 2009·The Journal of Biological Chemistry·Kaori K TakaiTitia de Lange
Dec 17, 2009·Genes & Development·Nausica ArnoultArturo Londoño-Vallejo

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Citations

Oct 25, 2013·Frontiers of Medicine·Yiming LuJing Ye
Aug 22, 2013·Molecular Therapy. Nucleic Acids·Amina BoussouarJing Ye
Mar 20, 2012·Nature Cell Biology·Marzia FumagalliFabrizio d'Adda di Fagagna
Nov 24, 2011·Nature Reviews. Molecular Cell Biology·Seychelle M VosJames M Berger
Nov 16, 2010·Nature Structural & Molecular Biology·Sophie BadieMadalena Tarsounas
Jun 17, 2011·The Journal of Biological Chemistry·Amadou BahRaymund J Wellinger
Jun 14, 2012·The Journal of Biological Chemistry·Blanka SengerováPeter J McHugh
Dec 6, 2011·Nucleic Acids Research·Anaïs PouletMarie-Josèphe Giraud-Panis
Nov 18, 2010·BMC Biochemistry·Hui-I Kao Tom, Carol W Greider
Apr 29, 2011·PloS One·Asmaa M BakerTerace M Fletcher
Nov 29, 2012·PloS One·Jay R Stringer, Christopher M Counter
Jul 11, 2013·PloS One·Géraldine PottierLaure Sabatier
Jul 15, 2011·Clinical and Experimental Gastroenterology·Claire M PayneHarris Bernstein
Jan 8, 2014·Nucleic Acids Research·Emilie FalletMaria Teresa Teixeira
Jun 11, 2014·Nature Reviews. Genetics·Jing YeEric Gilson
Aug 31, 2014·Trends in Cell Biology·Roderick J O'Sullivan, Genevieve Almouzni
Oct 6, 2015·International Journal of Cancer. Journal International Du Cancer·Leilei ZhangXianqun Fan
Aug 11, 2010·FEBS Letters·Marie-Josèphe Giraud-PanisEric Gilson
Jan 26, 2016·Trends in Biochemical Sciences·Ilaria PettinatiChristopher J Schofield
Jan 18, 2016·Molecular Cell·Delphine Benarroch-PopivkerMarie-Josèphe Giraud-Panis
Jan 10, 2016·Nucleic Acids Research·Guillaume GaullierMarie-Hélène Le Du
Mar 20, 2013·EMBO Reports·Kerstin BauerK Lenhard Rudolph
Dec 3, 2010·Journal of Cellular and Molecular Medicine·Shilpa Sampathi, Weihang Chai
Jul 21, 2015·Trends in Biochemical Sciences·Paula Martínez, Maria A Blasco
May 23, 2015·Nucleic Acids Research·Alessandra GalatiStefano Cacchione
Nov 29, 2014·Chromosoma·Eliana M C Tacconi, Madalena Tarsounas
Nov 22, 2011·Cell Cycle·Blanka SengerováPeter J McHugh
Jul 9, 2011·Nucleus·Raffaella Diotti, Diego Loayza
Mar 14, 2012·Methods : a Companion to Methods in Enzymology·Angela RizzoAnnamaria Biroccio
Sep 6, 2012·Current Opinion in Cell Biology·Anthony J Cesare, Jan Karlseder
Apr 8, 2015·Trends in Biochemical Sciences·Sascha FeuerhahnAntonio Porro
Sep 14, 2010·Molecular Cell·Marie-Josèphe Giraud-PanisEric Gilson

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