Maria A Blasco

Summary

Country: Spain

Publications

  1. pmc Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs
    Silvia Espejel
    Molecular Oncology Program, Spanish National Cancer Center CNIO, E 28029 Madrid, Spain
    J Cell Biol 167:627-38. 2004
  2. pmc ATR suppresses telomere fragility and recombination but is dispensable for elongation of short telomeres by telomerase
    Carolyn J McNees
    Telomeres and Telomerase Group, Spanish National Cancer Centre, Madrid 28029, Spain
    J Cell Biol 188:639-52. 2010
  3. pmc Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer
    Bruno Bernardes de Jesus
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    EMBO Mol Med 4:691-704. 2012
  4. pmc Suv4-20h abrogation enhances telomere elongation during reprogramming and confers a higher tumorigenic potential to iPS cells
    Rosa M Marion
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernandez Almagro 3, Madrid, Spain
    PLoS ONE 6:e25680. 2011
  5. pmc SIRT1 contributes to telomere maintenance and augments global homologous recombination
    Jose A Palacios
    Telomeres and Telomerase Group, Spanish National Cancer Centre, Madrid E 28029, Spain
    J Cell Biol 191:1299-313. 2010
  6. pmc Suv4-20h deficiency results in telomere elongation and derepression of telomere recombination
    Roberta Benetti
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain
    J Cell Biol 178:925-36. 2007
  7. pmc 53BP1 deficiency combined with telomere dysfunction activates ATR-dependent DNA damage response
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Research Centre, E 28029 Madrid, Spain
    J Cell Biol 197:283-300. 2012
  8. pmc Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity
    Elsa Vera
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre, Melchor Fernandez Almagro 3, Madrid, Spain
    PLoS ONE 8:e53760. 2013
  9. pmc Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres
    Irene Siegl-Cachedenier
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E 28029, Spain
    J Cell Biol 179:277-90. 2007
  10. pmc A p53-dependent response limits epidermal stem cell functionality and organismal size in mice with short telomeres
    Ignacio Flores
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    PLoS ONE 4:e4934. 2009

Collaborators

Detail Information

Publications87

  1. pmc Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs
    Silvia Espejel
    Molecular Oncology Program, Spanish National Cancer Center CNIO, E 28029 Madrid, Spain
    J Cell Biol 167:627-38. 2004
    ..These results support the notion that absence of telomerase and short telomeres in combination with DNA repair deficiencies accelerate the aging process without impacting on tumorigenesis...
  2. pmc ATR suppresses telomere fragility and recombination but is dispensable for elongation of short telomeres by telomerase
    Carolyn J McNees
    Telomeres and Telomerase Group, Spanish National Cancer Centre, Madrid 28029, Spain
    J Cell Biol 188:639-52. 2010
    ..These results reveal a previously unnoticed role for mammalian ATR in telomere protection and stability...
  3. pmc Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer
    Bruno Bernardes de Jesus
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    EMBO Mol Med 4:691-704. 2012
    ....
  4. pmc Suv4-20h abrogation enhances telomere elongation during reprogramming and confers a higher tumorigenic potential to iPS cells
    Rosa M Marion
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernandez Almagro 3, Madrid, Spain
    PLoS ONE 6:e25680. 2011
    ....
  5. pmc SIRT1 contributes to telomere maintenance and augments global homologous recombination
    Jose A Palacios
    Telomeres and Telomerase Group, Spanish National Cancer Centre, Madrid E 28029, Spain
    J Cell Biol 191:1299-313. 2010
    ..These findings link SIRT1 to telomere biology and global DNA repair and provide new mechanistic explanations for the known functions of SIRT1 in protection from DNA damage and some age-associated pathologies...
  6. pmc Suv4-20h deficiency results in telomere elongation and derepression of telomere recombination
    Roberta Benetti
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain
    J Cell Biol 178:925-36. 2007
    ..These results demonstrate the importance of chromatin architecture in the maintenance of telomere length homeostasis and reveal a novel role for histone lysine methylation in controlling telomere recombination...
  7. pmc 53BP1 deficiency combined with telomere dysfunction activates ATR-dependent DNA damage response
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Research Centre, E 28029 Madrid, Spain
    J Cell Biol 197:283-300. 2012
    ..In intact mice, combined 53BP1/TRF1 deficiency in stratified epithelia resulted in earlier onset of DNA damage and increased CHK1 phosphorylation during embryonic development, leading to aggravation of skin phenotypes...
  8. pmc Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity
    Elsa Vera
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre, Melchor Fernandez Almagro 3, Madrid, Spain
    PLoS ONE 8:e53760. 2013
    ..These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing "health span" and extending mouse longevity...
  9. pmc Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres
    Irene Siegl-Cachedenier
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E 28029, Spain
    J Cell Biol 179:277-90. 2007
    ..Additionally, telomerase reintroduction into these mice results in a normal life span by preventing degenerative pathologies in the absence of increased tumorigenesis...
  10. pmc A p53-dependent response limits epidermal stem cell functionality and organismal size in mice with short telomeres
    Ignacio Flores
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    PLoS ONE 4:e4934. 2009
    ....
  11. pmc A 'higher order' of telomere regulation: telomere heterochromatin and telomeric RNAs
    Stefan Schoeftner
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    EMBO J 28:2323-36. 2009
    ..We will also discuss the links between epigenetic alterations at mammalian telomeres and telomere-associated diseases...
  12. pmc Telomeres in cancer and ageing
    Luis E Donate
    Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Research Centre CNIO, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain
    Philos Trans R Soc Lond B Biol Sci 366:76-84. 2011
    ..These new mouse models, together with the telomerase-deficient mouse model, are valuable tools for understanding human pathologies produced by telomere dysfunction...
  13. pmc Beyond average: potential for measurement of short telomeres
    Elsa Vera
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, E 28029, Spain
    Aging (Albany NY) 4:379-92. 2012
    ..The information provided by each method and their suitability for different studies is discussed here...
  14. doi request reprint Assessing cell and organ senescence biomarkers
    Bruno Bernardes de Jesus
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain
    Circ Res 111:97-109. 2012
    ..Here, we focus on the current methods to assess cellular senescence, discriminating the advantages and disadvantages of several senescence biomarkers...
  15. ncbi request reprint The epigenetic regulation of mammalian telomeres
    Maria A Blasco
    Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Centre CNIO, 3 Melchor Fernandez Almagro, Madrid E 28029, Spain
    Nat Rev Genet 8:299-309. 2007
    ..These links between epigenetic status and telomere-length regulation provide important new avenues for understanding processes such as cancer development and ageing, which are characterized by telomere-length defects...
  16. ncbi request reprint Telomeres and human disease: ageing, cancer and beyond
    Maria A Blasco
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 28029 Madrid, Spain
    Nat Rev Genet 6:611-22. 2005
    ..These findings have inspired a number of potential therapeutic strategies that are based on telomerase and telomeres...
  17. pmc Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging
    Maria A Blasco
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    EMBO J 24:1095-103. 2005
    ..Here, I will discuss how these different mouse models have contributed to our understanding on the role of telomeres and telomerase in cancer and aging...
  18. ncbi request reprint Telomere length, stem cells and aging
    Maria A Blasco
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, 3 Melchor Fernandez Almagro, 28019 Madrid, Spain
    Nat Chem Biol 3:640-9. 2007
    ..Here, we will review the current evidence linking telomere shortening to aging and stem cell dysfunction...
  19. ncbi request reprint Carcinogenesis Young Investigator Award. Telomere epigenetics: a higher-order control of telomere length in mammalian cells
    Maria A Blasco
    Molecular Oncology Program, Spanish National Cancer Centre CNIO, E 28029 Madrid, Spain
    Carcinogenesis 25:1083-7. 2004
    ..Here, we will discuss recent findings suggesting that telomeric chromatin shares many features with pericentric chromatin, and that disruption of telomeric heterochromatin results in changes in telomere length...
  20. ncbi request reprint Mammalian telomeres and telomerase: why they matter for cancer and aging
    Maria A Blasco
    Department of Immunology and Oncology, National Centre of Biotechnology, Madrid, Spain
    Eur J Cell Biol 82:441-6. 2003
    ..This review focuses on the analysis of different mouse models for proteins that are important for telomere function, which have highlighted the importance of telomeres and telomerase for cancer and aging...
  21. pmc Functional interaction between DNA-PKcs and telomerase in telomere length maintenance
    Silvia Espejel
    Department of Immunology and Oncology, National Centre of Biotechnology, E 28049 Madrid, Spain
    EMBO J 21:6275-87. 2002
    ..These results suggest a critical role of DNA-PKcs in both cancer and aging...
  22. doi request reprint Telomerase reverse transcriptase delays aging in cancer-resistant mice
    Antonia Tomás-Loba
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    Cell 135:609-22. 2008
    ..These results demonstrate that constitutive expression of Tert provides antiaging activity in the context of a mammalian organism...
  23. pmc Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid E 28029, Spain
    Genes Dev 23:2060-75. 2009
    ....
  24. pmc Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice
    Silvia Espejel
    Molecular Oncology Program, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, E 28029, Madrid, Spain
    EMBO Rep 5:503-9. 2004
    ..In conclusion, these data link the dual role of DNA-PKcs in DNA repair and telomere length maintenance to organismal ageing and cancer...
  25. pmc TRF1 controls telomere length and mitotic fidelity in epithelial homeostasis
    Purificación Muñoz
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 28029 Madrid, Spain
    Mol Cell Biol 29:1608-25. 2009
    ..Together, these results demonstrate that TRF1, like TRF2, negatively regulates telomere length in vivo by controlling the action of the XPF nuclease at telomeres; in addition, TRF1 has a unique role in the mitotic spindle checkpoint...
  26. ncbi request reprint Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin
    Susana Gonzalo
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid E 28029, Spain
    Nat Cell Biol 7:420-8. 2005
    ..These observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin...
  27. pmc TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice
    Agueda M Tejera
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, Madrid E 28029, Spain
    Dev Cell 18:775-89. 2010
    ..These results suggest a telomere-capping model where TPP1 protects telomere integrity and regulates telomerase recruitment to telomeres, thereby preventing early occurrence of degenerative pathologies...
  28. doi request reprint TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells
    Ralph P Schneider
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    Nat Commun 4:1946. 2013
    ..We further show that TRF1 is necessary for both induction and maintenance of pluripotency, and that TRF1 is a direct transcriptional target of Oct3/4...
  29. doi request reprint Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells
    Rosa M Marion
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernandez Almagro 3, Madrid, Spain
    Cell Stem Cell 4:141-54. 2009
    ..Together, these results highlight the importance of telomere biology for iPS cell generation and functionality...
  30. pmc Telomere shortening relaxes X chromosome inactivation and forces global transcriptome alterations
    Stefan Schoeftner
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid 28029, Spain
    Proc Natl Acad Sci U S A 106:19393-8. 2009
    ....
  31. pmc Increased p53 activity does not accelerate telomere-driven ageing
    Isabel Garcia-Cao
    Tumor Suppression Group, Spanish National Cancer Center, Madrid
    EMBO Rep 7:546-52. 2006
    ..From these observations, we conclude that p53 has an active role in eliminating telomere-damaged cells, and we exclude the possibility of an age-promoting effect of p53 on telomere-driven ageing...
  32. pmc Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre CNIO, Melchor Fernandez Almagro 3, Madrid, E 28029, Spain
    Nat Cell Biol 12:768-80. 2010
    ..These findings place a telomere protein at the interface between telomere function and transcriptional regulation...
  33. pmc Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis
    Raquel Blanco
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid 28029, Spain
    Genes Dev 21:206-20. 2007
    ..These results are of particular relevance given that TRF2 is up-regulated in some human cancers. Furthermore, these data suggest that telomerase inhibition might not be effective to cease the growth of TRF2-overexpressing tumors...
  34. pmc Deficient mismatch repair improves organismal fitness and survival of mice with dysfunctional telomeres
    Irene Siegl-Cachedenier
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid 28029, Spain
    Genes Dev 21:2234-47. 2007
    ..These results highlight an unprecedented role for MMR in mediating the cellular response to dysfunctional telomeres in vivo by attenuating p21 induction...
  35. ncbi request reprint Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II
    Stefan Schoeftner
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 28029 Madrid, Spain
    Nat Cell Biol 10:228-36. 2008
    ..Our results indicate that TelRNAs are novel components of mammalian telomeres, which are anticipated to be fundamental for understanding telomere biology and telomere-related diseases, such as cancer and ageing...
  36. doi request reprint MSH2 deficiency abolishes the anticancer and pro-aging activity of short telomeres
    Paula Martinez
    Spanish National Cancer Centre, Madrid, Spain
    Aging Cell 8:2-17. 2009
    ..These results highlight a role for MSH2 in the organismal response to dysfunctional telomeres, which in turn may be important in the pathobiology of human cancers bearing mutations in the MMR pathway...
  37. pmc A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
    Rosa M Marion
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre CNIO, Melchor Fernandez Almagro 3, Madrid E 28029, Spain
    Nature 460:1149-53. 2009
    ....
  38. ncbi request reprint Effects of telomerase and telomere length on epidermal stem cell behavior
    Ignacio Flores
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, Madrid E 28029, Spain
    Science 309:1253-6. 2005
    ..The effects of telomeres and telomerase on stem cell biology anticipate their role in cancer and aging...
  39. pmc Centromere mitotic recombination in mammalian cells
    Isabel Jaco
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, 28029 Madrid, Spain
    J Cell Biol 181:885-92. 2008
    ....
  40. ncbi request reprint Identification of telomere-dependent "senescence-like" arrest in mouse embryonic fibroblasts
    Silvia Espejel
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Campus Cantoblanco, Madrid, Spain
    Exp Cell Res 276:242-8. 2002
    ..In summary, we have identified here two different ways to induce a telomere-dependent senescence-like arrest in MEF...
  41. ncbi request reprint Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice
    Eva Gonzalez-Suarez
    Molecular Oncology Program, Spanish National Cancer Centre, E 28029 Madrid, Spain
    Oncogene 24:2256-70. 2005
    ..These findings indicate that telomerase overexpression extends the maximum lifespan of mice...
  42. ncbi request reprint Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres
    Roberta Benetti
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 28029 Madrid, Spain
    Nat Genet 39:243-50. 2007
    ..These observations highlight the importance of telomere repeats in the establishment of constitutive heterochromatin at mammalian telomeres and subtelomeres and point to histone modifications as important in counting telomere repeats...
  43. ncbi request reprint Role of TRF2 in the assembly of telomeric chromatin
    Roberta Benetti
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    Cell Cycle 7:3461-8. 2008
    ..Telomere shortening in K5TRF2 mice is also accompanied by decreased abundance of telomeric transcripts. Together, these findings indicate a previously unnoticed role for TRF2 in the assembly of telomeric chromatin...
  44. pmc The telomerase RNA component Terc is required for the tumour-promoting effects of Tert overexpression
    Maria Luisa Cayuela
    Molecular Oncology Program, Spanish National Cancer Center CNIO, 28029 Madrid, Spain
    EMBO Rep 6:268-74. 2005
    ..These findings highlight Terc as a target for telomerase-based anticancer therapies...
  45. pmc "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally
    Isabel Garcia-Cao
    Spanish National Center of Biotechnology, Department of Immunology and Oncology, Campus de Cantoblanco, Madrid E 28049, Spain
    EMBO J 21:6225-35. 2002
    ..Together, our results prove that cancer resistance can be enhanced by a simple genetic modification and in the absence of undesirable effects...
  46. pmc Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres
    Silvia Espejel
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Madrid E 28049, Spain
    EMBO J 21:2207-19. 2002
    ....
  47. pmc A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases
    Roberta Benetti
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 3 Melchor Fernandez Almagro, Madrid E 28029, Spain
    Nat Struct Mol Biol 15:268-79. 2008
    ..These results identify a pathway by which miR-290 directly regulates Rbl2-dependent Dnmt expression, indirectly affecting telomere-length homeostasis...
  48. ncbi request reprint Telomere dynamics in Fancg-deficient mouse and human cells
    Sonia Franco
    Molecular Oncology Program, Spanish National Cancer Centre, 3 Melchor Fernandez Almagro, 28029 Madrid, Spain
    Blood 104:3927-35. 2004
    ..These findings suggest that telomerase-based therapies could be useful prophylactic agents in FA aplastic anemia by preserving their telomere reserve in the context of the disease...
  49. ncbi request reprint Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models
    Sonia Franco
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain
    Carcinogenesis 26:1613-26. 2005
    ....
  50. pmc Genetic analysis of myc and telomerase interactions in vivo
    Ignacio Flores
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    Mol Cell Biol 26:6130-8. 2006
    ..Taken together, these results highlight telomerase as a mediator of Myc-induced papillomatosis and suggest telomerase as a putative therapeutic target for Myc-dependent lesions...
  51. ncbi request reprint DNA methyltransferases control telomere length and telomere recombination in mammalian cells
    Susana Gonzalo
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid E 28029, Spain
    Nat Cell Biol 8:416-24. 2006
    ..Together, these results demonstrate a previously unappreciated role for DNA methylation in maintaining telomere integrity...
  52. pmc Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice
    Andres Canela
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 28029 Madrid, Spain
    Mol Cell Biol 24:4275-93. 2004
    ....
  53. ncbi request reprint XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer
    Purificación Muñoz
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain
    Nat Genet 37:1063-71. 2005
    ..Finally, we show that a number of human skin tumors have increased expression of TRF2, further highlighting a role for TRF2 in skin cancer...
  54. doi request reprint The role of telomeres and telomerase in stem cell aging
    Ignacio Flores
    Cardiovascular Development Biology Program, Spanish National Cardiovascular Research Centre CNIC, Madrid, Spain
    FEBS Lett 584:3826-30. 2010
    ..During the last years it has become evident that telomeres and telomerase are main components of the stem cell "ignition" mechanism, providing a way to restrain cancer and delay aging...
  55. pmc Genetic dissection of the mechanisms underlying telomere-associated diseases: impact of the TRF2 telomeric protein on mouse epidermal stem cells
    Gerdine J Stout
    Spanish National Cancer Research Center, Madrid, Spain
    Dis Model Mech 2:139-56. 2009
    ....
  56. pmc Role of mammalian Rad54 in telomere length maintenance
    Isabel Jaco
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Madrid E 28049, Spain
    Mol Cell Biol 23:5572-80. 2003
    ..Finally, the study of mice doubly deficient for Rad54 and DNA-PKcs showed that telomere fusions due to DNA-PKcs deficiency were not rescued in the absence of Rad54, suggesting that they are not mediated by Rad54 activity...
  57. pmc Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita
    Fabian Beier
    Telomere and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    Blood 120:2990-3000. 2012
    ..Together, these results represent proof of principle that mutations in TRF1 lead to the main clinical features of BMF...
  58. pmc The Ink4/Arf locus is a barrier for iPS cell reprogramming
    Han Li
    Tumor Suppression Group, Spanish National Cancer Research Centre CNIO, 3 Melchor Fernandez Almagro Street, Madrid E 28029, Spain
    Nature 460:1136-9. 2009
    ..All together, we conclude that the silencing of Ink4/Arf locus is rate-limiting for reprogramming, and its transient inhibition may significantly improve the generation of iPS cells...
  59. pmc The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence
    Bruno Bernardes de Jesus
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernandez Almagro 3, Madrid, Spain
    Aging Cell 10:604-21. 2011
    ..Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence...
  60. ncbi request reprint Delayed ageing through damage protection by the Arf/p53 pathway
    Ander Matheu
    Tumor Suppression Group, Spanish National Cancer Research Centre CNIO, Madrid 28029, Spain
    Nature 448:375-9. 2007
    ..These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity...
  61. ncbi request reprint A role for the Rb family of proteins in controlling telomere length
    Marta García-Cao
    Department of Immunology and Oncology, National Center of Biotechnology, E 28049 Madrid, Spain
    Nat Genet 32:415-9. 2002
    ..These findings demonstrate a connection between the Rb1 family and the control of telomere length in mammalian cells...
  62. ncbi request reprint Role of the TRF2 telomeric protein in cancer and ageing
    Purificación Muñoz
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    Cell Cycle 5:718-21. 2006
    ..K5-TRF2 mice represent a new tool to understand the consequences of critical telomere shortening a telomerase-proficient genetic background, more closely resembling human cancer and aging pathologies...
  63. pmc The longest telomeres: a general signature of adult stem cell compartments
    Ignacio Flores
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid E 28029, Spain
    Genes Dev 22:654-67. 2008
    ....
  64. ncbi request reprint Role of human Ku86 in telomere length maintenance and telomere capping
    Isabel Jaco
    Molecular Oncology Program, Spanish National Cancer Center CNIO, Madrid, Spain
    Cancer Res 64:7271-8. 2004
    ..These findings demonstrate a role for Ku86 in regulating telomere length and telomere capping in human cells, which, in turn, could impact on cancer and aging...
  65. ncbi request reprint Many ways to telomere dysfunction: in vivo studies using mouse models
    Fermín A Goytisolo
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Campus Cantoblanco, E 28049, Madrid, Spain
    Oncogene 21:584-91. 2002
    ..These murine models are helping us to understand the consequences of telomere dysfunction for cancer, aging and DNA repair, as well as, the molecular mechanisms by which telomeres exert their protective function...
  66. ncbi request reprint Immunosenescence phenotypes in the telomerase knockout mouse
    Maria A Blasco
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Campus Cantoblanco, 28049, Madrid, Spain
    Springer Semin Immunopathol 24:75-85. 2002
    ..Both immune system defects are landmarks of immunosenescence. The study of the telomerase-deficient mouse model supports the notion that telomere shortening with age contributes to immunological dysfunction in the elderly...
  67. pmc Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres
    Silvia Remeseiro
    Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    EMBO J 31:2076-89. 2012
    ..We propose a novel mechanism for aneuploidy generation that involves impaired telomere replication upon loss of cohesin-SA1, with clear implications in tumourigenesis...
  68. ncbi request reprint Telomere dysfunction results in enhanced organismal sensitivity to the alkylating agent N-methyl-N-nitrosourea
    Eva Gonzalez-Suarez
    Department of Immunology and Oncology, National Center of Biotechnology, Madrid, Spain
    Cancer Res 63:7047-50. 2003
    ..Finally, G5 Terc(-/-) hypersensitivity to MNU supports the notion that short telomeres interfere with proper DNA damage repair...
  69. ncbi request reprint Telomerase regulation and stem cell behaviour
    Ignacio Flores
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 28029 Madrid, Spain
    Curr Opin Cell Biol 18:254-60. 2006
    ..More recently, the role of telomerase and telomere length in stem cells is starting to be elucidated...
  70. pmc A metabolic signature predicts biological age in mice
    Antonia Tomás-Loba
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre CNIO, Melchor Fernandez Almagro 3, Madrid, E 28029, Spain
    Aging Cell 12:93-101. 2013
    ..These results indicate that the metabolomic signature is associated with the biological age rather than with the chronological age. This constitutes one of the first aging-associated metabolomic signatures in a mammalian organism...
  71. doi request reprint The rate of increase of short telomeres predicts longevity in mammals
    Elsa Vera
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Center, Melchor Fernandez Almagro 3, E 28029 Madrid, Spain
    Cell Rep 2:732-7. 2012
    ..These findings demonstrate that short telomeres have a direct impact on longevity in mammals, and they highlight the importance of performing longitudinal telomere studies to predict longevity...
  72. doi request reprint Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, Madrid E 28029, Spain
    Nat Rev Cancer 11:161-76. 2011
    ..This Review discusses the role of telomeric proteins in cancer and ageing through modulating telomere length and protection, as well as regulating gene expression by binding to non-telomeric sites...
  73. doi request reprint Chromatin regulation and non-coding RNAs at mammalian telomeres
    Stefan Schoeftner
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain
    Semin Cell Dev Biol 21:186-93. 2010
    ..Understanding the links between the epigenetic status of telomeres, TERRA/TelRNA and telomere homeostasis will open new avenues for our understanding of organismal development, cancer and ageing...
  74. pmc Different telomere-length dynamics at the inner cell mass versus established embryonic stem (ES) cells
    Elisa Varela
    Telomeres and Telomerase Group, Spanish National Cancer Research Centre, Madrid E 28029, Spain
    Proc Natl Acad Sci U S A 108:15207-12. 2011
    ....
  75. ncbi request reprint Mammalian meiotic telomeres: composition and ultrastructure in telomerase-deficient mice
    Sonia Franco
    Department of Immunology and Oncology, National Centre of Biotechnology, CSIC, Madrid, Spain
    Eur J Cell Biol 81:335-40. 2002
    ..These results suggest, as already shown in yeast, that most telomere chromatin is dispensable for proper attachment of mammalian meiotic chromosome ends to the nuclear envelope...
  76. doi request reprint Telomere rejuvenation during nuclear reprogramming
    Rosa M Marion
    Spanish National Cancer Centre, Madrid, Spain
    Curr Opin Genet Dev 20:190-6. 2010
    ..These findings also revealed that the structure of telomeric chromatin is dynamic and controlled by epigenetic programmes, which are reversed by reprogramming...
  77. ncbi request reprint Telomeres in cancer and aging: lessons from the mouse
    Maria A Blasco
    Department of Immunology and Oncology, National Centre of Biotechnology, E 28049, Madrid, Spain
    Cancer Lett 194:183-8. 2003
    ..Here, I will discuss these studies, as well as their implications for putative therapies based of telomerase inhibition of telomerase re-introduction for cancer or age-related diseases, respectively...
  78. pmc Global chromatin compaction limits the strength of the DNA damage response
    Matilde Murga
    Genomic Instability Group, Molecular Oncology Programme, Spanish National Cancer Center, Madrid 28029, Spain
    J Cell Biol 178:1101-8. 2007
    ..We propose that slight differences in the epigenetic configuration might account for the cell-to-cell variation in the strength of the DDR observed when groups of cells are challenged with DNA breaks...
  79. pmc High-throughput telomere length quantification by FISH and its application to human population studies
    Andres Canela
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, 3 Melchor Fernandez Almagro, Madrid E 28029, Spain
    Proc Natl Acad Sci U S A 104:5300-5. 2007
    ..We show here that this technique provides the accuracy and sensitivity to uncover associations between telomere length and human disease...
  80. pmc Cooperation between p53 mutation and high telomerase transgenic expression in spontaneous cancer development
    Eva Gonzalez-Suarez
    Department of Immunology and Oncology, National Center for Biotechnology, E 28049 Madrid, Spain
    Mol Cell Biol 22:7291-301. 2002
    ..Altogether, these results demonstrate that constitutive high levels of telomerase activity result in a decreased life span associated with an increased incidence of neoplasias as the organism ages...
  81. ncbi request reprint Mouse models to study the role of telomeres in cancer, aging and DNA repair
    Maria A Blasco
    Department of Immunology and Oncology, National Centre of Biotechnology, E 28049, Madrid, Spain
    Eur J Cancer 38:2222-8. 2002
    ..These mouse models have allowed the relevance of telomeres and telomerase in tumour development and the aging of the organism to be directly tested...
  82. ncbi request reprint Cancer and ageing: convergent and divergent mechanisms
    Manuel Serrano
    Spanish National Cancer Research Centre CNIO, 3 Melchor Fernandez Almagro Street, Madrid E 28029, Spain
    Nat Rev Mol Cell Biol 8:715-22. 2007
    ..The overall balance between these convergent and divergent mechanisms guarantees fitness and a cancer-free life until late adulthood for most individuals...
  83. ncbi request reprint Cellular senescence in cancer and aging
    Manuel Collado
    Spanish National Cancer Research Center CNIO, Madrid, Spain
    Cell 130:223-33. 2007
    ..Together these mechanisms limit excessive or aberrant cellular proliferation, and so the state of senescence protects against the development of cancer. Recent evidence suggests that cellular senescence also may be involved in aging...
  84. ncbi request reprint Novel roles for telomerase in aging
    Christoph Geserick
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain
    Mech Ageing Dev 127:579-83. 2006
    ..The positive effects of telomerase on aging seem to come of the price of tumour promotion. These antagonistic roles of telomerase in aging and cancer may have important implications for putative telomerase based therapies...
  85. ncbi request reprint Evolving views of telomerase and cancer
    Maria A Blasco
    Department of Immunology and Oncology, National Centre of Biotechnology, Spanish Council for Scientific Research CSIC, Campus de Cantoblanco, Madrid E 28049, Spain
    Trends Cell Biol 13:289-94. 2003
    ..These recent developments indicate that our understanding of telomere biology remains incomplete and implicate additional complexity in the relationships among telomeres, telomerase and cancer...
  86. ncbi request reprint Telomere length analysis
    Andres Canela
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, Spain
    Methods Mol Biol 371:45-72. 2007
    ..Here, we describe the different methodologies recently developed for telomere length quantification, as well as their potential applications for human aging studies...
  87. ncbi request reprint Mice deficient in telomerase activity develop hypertension because of an excess of endothelin production
    Gema Pérez-Rivero
    Research Unit, Principe de Asturias Hospital, Alcala de Henares, Madrid, Spain
    Circulation 114:309-17. 2006
    ..Telomere shortening has been related to vascular dysfunction and hypertension. In the present study, we analyzed the influence of telomerase deficiency and telomere shortening on arterial pressure (AP)...