Research Topics
Genomes and Genes
| Titia de LangeSummaryAffiliation: The Rockefeller University Country: USA Publications
| Collaborators
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Detail Information
Publications
DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletionGiulia B Celli
Laboratory for Cell Biology and Genetic, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Nat Cell Biol 7:712-8. 2005..Thus, activation of the ATM kinase pathway at chromosome ends does not require overhang degradation or other overt DNA processing...- Shelterin: the protein complex that shapes and safeguards human telomeresTitia de Lange
The Rockefeller University, New York, New York 10021, USA
Genes Dev 19:2100-10. 2005..Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1... - TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeresJeffrey Zheng Sheng Ye
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 279:47264-71. 2004..The TIN2-mediated cooperative binding of TRF1 and TRF2 to telomeres has important implications for the mechanism of telomere length regulation and protection... - Tel2 regulates the stability of PI3K-related protein kinasesHiroyuki Takai
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Cell 131:1248-59. 2007..These data identify Tel2 as a highly conserved regulator of PIKK stability... 
Apollo contributes to G overhang maintenance and protects leading-end telomeresPeng Wu
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Mol Cell 39:606-17. 2010..These data establish that the telomeric overhang is required for the protection of telomeres from the DNA damage response...- Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signalAgnel Sfeir
The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Science 327:1657-61. 2010..The data reveal that HDR at telomeres can take place in the absence of DNA damage foci and underscore the functional compartmentalization within shelterin... - Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpointJoshua Silverman
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10021, USA
Genes Dev 18:2108-19. 2004..These data reveal that human Rif1 contributes to the ATM-mediated protection against DNA damage and point to a remarkable difference in the primary function of this protein in yeast and mammals... - Telomere protection by TPP1/POT1 requires tethering to TIN2Kaori K Takai
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USA
Mol Cell 44:647-59. 2011..Thus, while TIN2 has a minor contribution to the repression of ATM by TRF2, its major role is to stabilize TPP1/POT1a on the ss telomeric DNA, thereby allowing effective exclusion of RPA and repression of ATR signaling... - Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1Eros Lazzerini Denchi
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Nature 448:1068-71. 2007..The results reveal how mammalian telomeres use multiple mechanisms to avoid DNA damage surveillance and provide an explanation for the induction of replicative senescence and genome instability by shortened telomeres... - Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeresDirk Hockemeyer
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Cell 126:63-77. 2006..We conclude that mouse telomeres require two distinct POT1 proteins whereas human telomeres have one. Such divergence is unprecedented in mammalian chromosome biology and has implications for modeling human telomere biology in mice... - Removal of shelterin reveals the telomere end-protection problemAgnel Sfeir
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Science 336:593-7. 2012.... - Cell cycle control of telomere protection and NHEJ revealed by a ts mutation in the DNA-binding domain of TRF2Akimitsu Konishi
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10065, USA
Genes Dev 22:1221-30. 2008..In contrast, the processing of dysfunctional telomeres by NHEJ occurred primarily in G1, being repressed in S/G2 in a cyclin-dependent kinase (CDK)-dependent manner... - POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complexJeffrey Zheng Sheng Ye
Laboratory for Cell Biology and Genetics and Laboratory for Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York 10021, USA
Genes Dev 18:1649-54. 2004..Reduction of PIP1 or POT1 levels with shRNAs led to telomere elongation, indicating that PIP1 contributes to telomere length control through recruitment of POT1... - The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage responseJan Karlseder
Laboratory for Cell Biology and Genetics, Rockefeller University, New York, USA
PLoS Biol 2:E240. 2004.... - Telomere protection by mammalian Pot1 requires interaction with Tpp1Dirk Hockemeyer
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
Nat Struct Mol Biol 14:754-61. 2007.... - Cell cycle-dependent role of MRN at dysfunctional telomeres: ATM signaling-dependent induction of nonhomologous end joining (NHEJ) in G1 and resection-mediated inhibition of NHEJ in G2Nadya Dimitrova
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065 6399, USA
Mol Cell Biol 29:5552-63. 2009..Thus, the role of MRN at dysfunctional telomeres is multifaceted, involving both repression of NHEJ in G(2) through end resection and induction of NHEJ in G(1) through ATM-dependent signaling... - No overt nucleosome eviction at deprotected telomeresPeng Wu
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Mol Cell Biol 28:5724-35. 2008..We conclude that ATM signaling, ATR signaling, NHEJ, and HR at deprotected telomeres can take place in the absence of overt nucleosome eviction... - Functional dissection of human and mouse POT1 proteinsWilhelm Palm
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065 6399, USA
Mol Cell Biol 29:471-82. 2009..Thus, human POT1 combines the features of POT1a and POT1b... - Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombinationGiulia B Celli
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Nat Cell Biol 8:885-90. 2006..Therefore, Ku- and TRF2-mediated repression of homologous recombination is an important aspect of telomere protection... - The role of the poly(ADP-ribose) polymerase tankyrase1 in telomere length control by the TRF1 component of the shelterin complexJill R Donigian
Laboratory of Cell Biology and Genetics, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 282:22662-7. 2007..We propose that the tankyrase1-controlled telomere extension is a human-specific elaboration that allows additional control over telomere length in telomerase positive cells... - Telomere protection by TPP1 is mediated by POT1a and POT1bTatsuya Kibe
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065 6399, USA
Mol Cell Biol 30:1059-66. 2010..No additional telomere dysfunction phenotypes were observed, establishing that the main role of TPP1 is to allow POT1a and POT1b to protect chromosome ends... - 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobilityNadya Dimitrova
The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
Nature 456:524-8. 2008.... - Rap1 affects the length and heterogeneity of human telomeresBibo Li
The Rockefeller University, New York, New York 10021, USA
Mol Biol Cell 14:5060-8. 2003..Surprisingly, hRap1 alleles lacking the BRCT domain diminished the heterogeneity of human telomeres, indicating that hRap1 also plays a role in the regulation of telomere length distribution... - Mammalian telomeres resemble fragile sites and require TRF1 for efficient replicationAgnel Sfeir
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Cell 138:90-103. 2009..These results identify a second telomere replication problem that is solved by the shelterin component TRF1... - How telomeres solve the end-protection problemTitia de Lange
Laboratory of Cell Biology and Genetics, Rockefeller University, New York, NY 10021, USA
Science 326:948-52. 2009..Telomeres appear to be tailored to these variations, explaining their variable structure and composition... - Regulation of telomerase by telomeric proteinsAgata Smogorzewska
The Rockefeller University, New York, New York 10021, USA
Annu Rev Biochem 73:177-208. 2004..Here we discuss the details of telomerase and its regulation by the telomere... - MDC1 accelerates nonhomologous end-joining of dysfunctional telomeresNadya Dimitrova
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10021, USA
Genes Dev 20:3238-43. 2006..We propose that the binding of MDC1 to gamma-H2AX directly affects NHEJ in a manner that is independent of the ATM-dependent cell cycle arrest pathway... - In vivo stoichiometry of shelterin componentsKaori K Takai
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10065 6399, USA
J Biol Chem 285:1457-67. 2010..Finally, we report that a 10-fold reduction in TRF2 affects the regulation of telomere length but not the protection of telomeres in tumor cell lines... - POT1 as a terminal transducer of TRF1 telomere length controlDiego Loayza
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Nature 423:1013-8. 2003.... - TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complexJeffrey Zheng Sheng Ye
The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Nat Genet 36:618-23. 2004..These data identify TIN2 as a PARP modulator in the TRF1 complex and can explain how TIN2 contributes to the regulation of telomere length... - A Shld1-controlled POT1a provides support for repression of ATR signaling at telomeres through RPA exclusionYi Gong
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Mol Cell 40:377-87. 2010..In G1, the accumulation of RPA at dysfunctional telomeres was strikingly less, and POT1a was sufficient to repress ATR signaling. These results support an RPA exclusion model for the repression of ATR signaling at telomeres... - Homologous recombination generates T-loop-sized deletions at human telomeresRichard C Wang
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Cell 119:355-68. 2004..These findings show that t-loop deletion by HR influences the integrity and dynamics of mammalian telomeres... - Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phaseMegan Van Overbeek
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Curr Biol 16:1295-302. 2006..We propose that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection of telomeres during or after their replication... - Hepatocytes with extensive telomere deprotection and fusion remain viable and regenerate liver mass through endoreduplicationEros Lazzerini Denchi
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10021, USA
Genes Dev 20:2648-53. 2006..We conclude that nondividing hepatocytes can maintain and regenerate liver function despite substantial loss of telomere integrity... - ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomesXu Dong Zhu
The Rockefeller University, New York, NY 10021, USA
Mol Cell 12:1489-98. 2003.... - Engineered telomere degradation models dyskeratosis congenitaDirk Hockemeyer
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10065, USA
Genes Dev 22:1773-85. 2008..These results provide experimental support for the notion that DC is caused by telomere dysfunction, and demonstrate that key aspects of a human telomere-based disease can be modeled in the mouse... - DNA binding features of human POT1: a nonamer 5'-TAGGGTTAG-3' minimal binding site, sequence specificity, and internal binding to multimeric sitesDiego Loayza
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1320 York Avenue, New York, NY 10021, USA
J Biol Chem 279:13241-8. 2004..These data indicate that POT1 has a strong sequence preference for the human telomeric repeat tract and predict that POT1 can bind both the 3' telomeric overhang and the displaced TTAGGG repeats at the base of the t-loop... - Mammalian Rif1 contributes to replication stress survival and homology-directed repairSara B C Buonomo
Laboratory of Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USA
J Cell Biol 187:385-98. 2009..Collectively, these findings reveal a function for Rif1 in the repair of stalled forks by facilitating HDR... - Telomere-driven tetraploidization occurs in human cells undergoing crisis and promotes transformation of mouse cellsTeresa Davoli
Laboratory for Genetics and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Cancer Cell 21:765-76. 2012..These data establish that telomere-driven tetraploidization is induced by critically short telomeres and has the potential to promote tumorigenesis in early cancerous lesions... 
How shelterin protects mammalian telomeresWilhelm Palm
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
Annu Rev Genet 42:301-34. 2008..Recent experiments, discussed here, have revealed how shelterin represses the ATM and ATR kinase signaling pathways and hides chromosome ends from nonhomologous end joining and homology-directed repair...- Different telomere damage signaling pathways in human and mouse cellsAgata Smogorzewska
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, NY 10021, USA
EMBO J 21:4338-48. 2002..These findings reveal a fundamental difference in telomere damage signaling in human and mouse cells that bears on the use of mouse models for the telomere tumor suppressor pathway... - DNA damage foci at dysfunctional telomeresHiroyuki Takai
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
Curr Biol 13:1549-56. 2003..Furthermore, induction of TIFs through TRF2 inhibition provides an opportunity to study the DNA damage response within the context of well-defined, physically marked lesions... - POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes endDirk Hockemeyer
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
EMBO J 24:2667-78. 2005.... - Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexesHiroyuki Takai
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10065, USA
Genes Dev 24:2019-30. 2010..Taken together, our data suggest that the Tel2-Tti1-Tti2 complex is a PIKK-specific cochaperone for Hsp90... - Significant role for p16INK4a in p53-independent telomere-directed senescenceJacqueline J L Jacobs
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021 USA
Curr Biol 14:2302-8. 2004..We conclude that p16(INK4a) contributes to the p53-independent response to telomere damage... - DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2Agata Smogorzewska
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Curr Biol 12:1635-44. 2002..However, the molecular nature of these fusions and the mechanism by which they occur have not been elucidated... - Telomeric 3' overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CSTPeng Wu
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Cell 150:39-52. 2012..3' overhang formation is thus a multistep, shelterin-controlled process, ensuring functional telomeric overhangs at chromosome ends... - The causes and consequences of polyploidy in normal development and cancerTeresa Davoli
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USA
Annu Rev Cell Dev Biol 27:585-610. 2011..The origins of these polyploidization events and their consequences for tumor progression are explored in this review... - Senescence induced by altered telomere state, not telomere lossJan Karlseder
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Science 295:2446-9. 2002..Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA... - Lasker Laurels for telomeraseTitia de Lange
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
Cell 126:1017-20. 2006..This year the Lasker Foundation pays tribute to telomerase, a medically important enzyme required for chromosome stability and long-term cell proliferation... - Taking apart Rap1: an adaptor protein with telomeric and non-telomeric functionsShaheen Kabir
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY, USA
Cell Cycle 9:4061-7. 2010..The protean nature of Rap1 is best understood by viewing it as an adaptor that can mediate a variety of protein-protein and protein-DNA interactions depending on the organism and the complex in which it is functioning... - Human telomerase caught in the actPeng Wu
The Rockefeller University, New York, NY 10065, USA
Cell 138:432-4. 2009..Contrary to this view, Zhao et al. (2009) now show that telomerase in human cancer cells extends most telomeres during every S phase and that complementary strand synthesis does not immediately follow telomerase action... - Persistent telomere damage induces bypass of mitosis and tetraploidyTeresa Davoli
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Cell 141:81-93. 2010..These observations suggest a general mechanism for the induction of tetraploidization in the early stages of tumorigenesis when telomere dysfunction can result from excessive telomere shortening... - Telomerase regulation at the telomere: a binary switchDiego Loayza
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Cell 117:279-80. 2004..They show that short telomeres are elongated more frequently than long telomeres, arguing that telomeres switch between two states, one that allows telomere extension and one that does not... - Targeted deletion reveals an essential function for the telomere length regulator Trf1Jan Karlseder
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
Mol Cell Biol 23:6533-41. 2003..These data suggest that murine Trf1 has an essential function that is independent of telomere length regulation... - T-loops and the origin of telomeresTitia de Lange
Laboratory for Cell Biology and Genetics, Box 159, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Nat Rev Mol Cell Biol 5:323-9. 2004 - Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathwayCourtney A Lovejoy
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York, United States of America
PLoS Genet 8:e1002772. 2012..These attributes will facilitate the diagnosis and treatment of ALT positive human cancers... - Protection of mammalian telomeresTitia de Lange
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
Oncogene 21:532-40. 2002.... - A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteinsYong Chen
Department of Biological Chemistry, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
Science 319:1092-6. 2008..Conversely, the TRFH domain of TRF1, but not of TRF2, interacts with another shelterin-associated factor: PinX1... - p16INK4a as a second effector of the telomere damage pathwayJacqueline J L Jacobs
Deptartment of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Cell Cycle 4:1364-8. 2005..Here we discuss the significance of p16INK4a as a second effector of the telomere damage response...