R. Dkc1, Tinf2, and Terf1 are downregulated by murine p53. mRNAs for Dkc1, Rtel1, Tinf2, and Terf1 were quantified in p53 À/À , WT, and p53 D31/D31 MEFs, untreated or treated with 10 mM Nutlin for 24 hr. Results are from four independent experiments

+. Mean, . *. Sem-are-shown, N. Arai, D. Nomura, K. Yokota et al., 05; n.s., not significant by Student's t test. See also Figure S7 Immunologically distinct p53 molecules generated by alternative splicing, Mol. Cell. Biol, vol.6, pp.3232-3239, 1986.

M. Armanios and E. H. Blackburn, The telomere syndromes, Nature Reviews Genetics, vol.12, issue.10, pp.693-704, 2012.
DOI : 10.1128/MCB.24.15.6631-6634.2004

G. M. Baerlocher, I. Vulto, G. De-jong, and P. M. Lansdorp, Flow cytometry and FISH to measure the average length of telomeres (flow FISH), Nature Protocols, vol.222, issue.5, 2006.
DOI : 10.1016/0304-4165(70)90182-0

B. J. Ballew, M. Yeager, K. Jacobs, N. Giri, J. Boland et al., Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita, Human Genetics, vol.272, issue.4, pp.473-480, 2013.
DOI : 10.1126/science.272.5259.258

M. A. Blasco, H. W. Lee, M. P. Hande, E. Samper, P. M. Lansdorp et al., Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA, Cell, vol.91, issue.1, pp.25-34, 1997.
DOI : 10.1016/S0092-8674(01)80006-4
URL : http://doi.org/10.1016/s0092-8674(01)80006-4

C. A. Brady and L. D. Attardi, p53 at a glance, Journal of Cell Science, vol.123, issue.15, pp.2527-2532, 2010.
DOI : 10.1242/jcs.064501

W. Bruins, E. Zwart, L. D. Attardi, T. Iwakuma, E. M. Hoogervorst et al., Increased Sensitivity to UV Radiation in Mice with a p53 Point Mutation at Ser389, Molecular and Cellular Biology, vol.24, issue.20, pp.8884-8894, 2004.
DOI : 10.1128/MCB.24.20.8884-8894.2004

H. Ding, M. Schertzer, X. Wu, M. Gertsenstein, S. Selig et al., Regulation of Murine Telomere Length by Rtel, Cell, vol.117, issue.7, pp.873-886, 2004.
DOI : 10.1016/j.cell.2004.05.026
URL : http://doi.org/10.1016/j.cell.2004.05.026

M. Dumble, L. Moore, S. M. Chambers, H. Geiger, G. Van-zant et al., The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging, Blood, vol.109, issue.4, pp.1736-1742, 2007.
DOI : 10.1182/blood-2006-03-010413

J. M. Espinosa, Mechanisms of regulatory diversity within the p53 transcriptional network, Oncogene, vol.3, issue.29, pp.4013-4023, 2008.
DOI : 10.4161/cc.5.19.3266

L. Feng, T. Lin, H. Uranishi, W. Gu, and Y. Xu, Functional Analysis of the Roles of Posttranslational Modifications at the p53 C Terminus in Regulating p53 Stability and Activity, Molecular and Cellular Biology, vol.25, issue.13, pp.5389-5395, 2005.
DOI : 10.1128/MCB.25.13.5389-5395.2005

O. S. Foord, P. Bhattacharya, Z. Reich, and V. Rotter, p53 protein, Nucleic Acids Research, vol.19, issue.19, pp.5191-5198, 1991.
DOI : 10.1093/nar/19.19.5191

K. Fujita, I. Horikawa, A. M. Mondal, L. M. Jenkins, E. Appella et al., Positive feedback between p53 and TRF2 during telomere-damage signalling and cellular senescence, Nature Cell Biology, vol.50, issue.12, pp.1205-1212, 2010.
DOI : 10.1002/pmic.200800666
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470109

P. J. Hamard, D. J. Lukin, and J. J. Manfredi, p53 Basic C Terminus Regulates p53 Functions through DNA Binding Modulation of Subset of Target Genes, Journal of Biological Chemistry, vol.12, issue.26, pp.22397-22407, 2012.
DOI : 10.1038/sj.onc.1201631

H. He, Y. Wang, X. Guo, S. Ramchandani, J. Ma et al., Pot1b Deletion and Telomerase Haploinsufficiency in Mice Initiate an ATR-Dependent DNA Damage Response and Elicit Phenotypes Resembling Dyskeratosis Congenita, Molecular and Cellular Biology, vol.29, issue.1, pp.229-240, 2009.
DOI : 10.1128/MCB.01400-08
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612488

A. Herrera-merchan, C. Cerrato, G. Luengo, O. Dominguez, M. A. Piris et al., miR-33-mediated downregulation of p53 controls hematopoietic stem cell self-renewal, Cell Cycle, vol.9, issue.16, pp.3277-3285, 2010.
DOI : 10.4161/cc.9.16.12598

T. R. Hupp, D. W. Meek, C. A. Midgley, L. , and D. P. , Regulation of the specific DNA binding function of p53, Cell, vol.71, issue.5, pp.875-886, 1992.
DOI : 10.1016/0092-8674(92)90562-Q

M. D. Kaeser and R. D. Iggo, Chromatin immunoprecipitation analysis fails to support the latency model for regulation of p53 DNA binding activity in vivo, Proc. Natl. Acad. Sci. USA 99, pp.95-100, 2002.
DOI : 10.1101/gad.859201

K. A. Krummel, C. J. Lee, F. Toledo, and G. M. Wahl, The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation, Proc. Natl. Acad. Sci. USA, pp.10188-10193, 2005.
DOI : 10.1038/ncb1024

D. Lane and A. Levine, p53 Research: The Past Thirty Years and the Next Thirty Years, Cold Spring Harbor Perspectives in Biology, vol.2, issue.12, p.893, 2010.
DOI : 10.1101/cshperspect.a000893
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982174

G. A. Lang, T. Iwakuma, Y. A. Suh, G. Liu, V. A. Rao et al., Gain of Function of a p53 Hot Spot Mutation in a Mouse Model of Li-Fraumeni Syndrome, Cell, vol.119, issue.6, pp.861-872, 2004.
DOI : 10.1016/j.cell.2004.11.006

G. Liu, T. Terzian, S. Xiong, C. S. Van-pelt, A. Audiffred et al., The p53-Mdm2 network in progenitor cell expansion during mouse postnatal development, The Journal of Pathology, vol.10, issue.4, pp.360-368, 2007.
DOI : 10.3109/08830180109056725

D. Liu, L. Ou, G. D. Clemenson, . Jr, C. Chao et al., Puma is required for p53-induced depletion of adult stem cells, Nature Cell Biology, vol.2, issue.10, pp.993-998, 2010.
DOI : 10.1038/ncb2100

K. Lö-hr, C. Mö-ritz, A. Contente, and M. Dobbelstein, Mediates Negative Regulation of Transcription by p53, Journal of Biological Chemistry, vol.62, issue.35, pp.32507-32516, 2003.
DOI : 10.1038/sj.onc.1202986

D. Malkin, F. P. Li, L. C. Strong, J. F. Fraumeni, . Jr et al., Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms, Science, vol.250, issue.4985, pp.1233-1238, 1990.
DOI : 10.1126/science.1978757

K. A. Mcgowan, J. Z. Li, C. Y. Park, V. Beaudry, H. K. Tabor et al., Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects, Nature Genetics, vol.44, issue.8, pp.963-970, 2008.
DOI : 10.1093/hmg/ddl467

K. Mckinney, M. Mattia, V. Gottifredi, and C. Prives, p53 Linear Diffusion along DNA Requires Its C Terminus, Molecular Cell, vol.16, issue.3, pp.413-424, 2004.
DOI : 10.1016/j.molcel.2004.09.032

S. M. Mendrysa, M. K. Mcelwee, J. Michalowski, K. A. O-'leary, K. M. Young et al., mdm2 Is Critical for Inhibition of p53 during Lymphopoiesis and the Response to Ionizing Irradiation, Molecular and Cellular Biology, vol.23, issue.2, pp.462-472, 2003.
DOI : 10.1128/MCB.23.2.462-473.2003

K. D. Meyer, S. C. Lin, C. Bernecky, Y. Gao, and D. J. Taatjes, p53 activates transcription by directing structural shifts in Mediator, Nature Structural & Molecular Biology, vol.6, issue.6, pp.753-760, 2010.
DOI : 10.1128/MCB.14.10.7013
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932482

J. M. Nigro, S. J. Baker, A. C. Preisinger, J. M. Jessup, R. Hostetter et al., Mutations in the p53 gene occur in diverse human tumour types, Nature, vol.342, issue.6250, pp.705-708, 1989.
DOI : 10.1038/342705a0

K. P. Olive, D. A. Tuveson, Z. C. Ruhe, B. Yin, N. A. Willis et al., Mutant p53 Gain of Function in Two Mouse Models of Li-Fraumeni Syndrome, Cell, vol.119, issue.6, pp.847-860, 2004.
DOI : 10.1016/j.cell.2004.11.004

I. Ourliac-garnier and A. Vallejo, Telomere Strand-Specific Length Analysis by Fluorescent In Situ Hybridization (Q-CO-FISH), Methods Mol. Biol, vol.36, issue.6, pp.33-46, 2011.
DOI : 10.1002/(SICI)1097-0320(19990801)36:4<267::AID-CYTO1>3.0.CO;2-O

E. M. Parry, J. K. Alder, S. S. Lee, J. A. Phillips, J. E. Loyd et al., Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita, Journal of Medical Genetics, vol.48, issue.5, pp.327-333, 2011.
DOI : 10.1136/jmg.2010.085100

E. M. Parry, J. K. Alder, X. Qi, J. J. Chen, A. et al., Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase, Blood, vol.117, issue.21, pp.5607-5611, 2011.
DOI : 10.1182/blood-2010-11-322149

T. C. Pereboom, L. J. Van-weele, A. Bondt, and A. W. Macinnes, A zebrafish model of dyskeratosis congenita reveals hematopoietic stem cell formation failure resulting from ribosomal protein-mediated p53 stabilization, Blood, vol.118, issue.20, pp.5458-5465, 2011.
DOI : 10.1182/blood-2011-04-351460

M. V. Poyurovsky, C. Katz, O. Laptenko, R. Beckerman, M. Lokshin et al., The C terminus of p53 binds the N-terminal domain of MDM2, Nature Structural & Molecular Biology, vol.3, issue.8, pp.982-989, 2010.
DOI : 10.1101/gad.1795709

I. Simeonova, V. Lejour, B. Bardot, R. Bouarich-bourimi, A. Morin et al., Fuzzy Tandem Repeats Containing p53 Response Elements May Define Species-Specific p53 Target Genes, PLoS Genetics, vol.276, issue.6, 2012.
DOI : 10.1371/journal.pgen.1002731.s016
URL : http://doi.org/10.1371/journal.pgen.1002731

A. Tafvizi, F. Huang, A. R. Fersht, L. A. Mirny, and A. M. Van-oijen, A single-molecule characterization of p53 search on DNA, Proc. Natl. Acad, 2011.
DOI : 10.1073/pnas.0511130103

I. Takenaka, F. Morin, B. R. Seizinger, and N. Kley, Regulation of the Sequence-specific DNA Binding Function of p53 by Protein Kinase C and Protein Phosphatases, Journal of Biological Chemistry, vol.9, issue.10, pp.5405-5411, 1995.
DOI : 10.1016/S0960-9822(00)00195-0

T. Terzian, Y. Wang, C. S. Van-pelt, N. F. Box, E. L. Travis et al., Haploinsufficiency of Mdm2 and Mdm4 in Tumorigenesis and Development, Molecular and Cellular Biology, vol.27, issue.15, pp.5479-5485, 2007.
DOI : 10.1128/MCB.00555-06

F. Toledo and G. M. Wahl, Regulating the p53 pathway: in vitro hypotheses, in vivo veritas, Nature Reviews Cancer, vol.55, issue.12, pp.909-923, 2006.
DOI : 10.1002/gcc.20310

F. Toledo, K. A. Krummel, C. J. Lee, C. W. Liu, L. W. Rodewald et al., A mouse p53 mutant lacking the proline-rich domain rescues Mdm4 deficiency and provides insight into the Mdm2-Mdm4-p53 regulatory network, Cancer Cell, vol.9, issue.4, pp.273-285, 2006.
DOI : 10.1016/j.ccr.2006.03.014

F. Toledo, C. W. Liu, C. J. Lee, and G. M. Wahl, RMCE-ASAP: a gene targeting method for ES and somatic cells to accelerate phenotype analyses, Nucleic Acids Research, vol.34, issue.13, p.92, 2006.
DOI : 10.1093/nar/gkl518
URL : http://doi.org/10.1093/nar/gkl518

A. Ventura, D. G. Kirsch, M. E. Mclaughlin, D. A. Tuveson, J. Grimm et al., Restoration of p53 function leads to tumour regression in vivo, Nature, vol.119, issue.7128, pp.661-665, 2007.
DOI : 10.1038/nature05541

T. J. Vulliamy, M. J. Kirwan, R. Beswick, U. Hossain, C. Baqai et al., Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations, PLoS ONE, vol.37, issue.9, 2011.
DOI : 10.1371/journal.pone.0024383.s004

A. J. Walne, T. Vulliamy, M. Kirwan, V. Plagnol, and I. Dokal, Constitutional Mutations in RTEL1 Cause Severe Dyskeratosis Congenita, The American Journal of Human Genetics, vol.92, issue.3, pp.448-453, 2013.
DOI : 10.1016/j.ajhg.2013.02.001
URL : http://doi.org/10.1016/j.ajhg.2013.02.001

Y. V. Wang, M. Leblanc, N. Fox, J. H. Mao, K. L. Tinkum et al., Fine-tuning p53 activity through C-terminal modification significantly contributes to HSC homeostasis and mouse radiosensitivity, Genes & Development, vol.25, issue.13, pp.1426-1438, 2011.
DOI : 10.1101/gad.2024411
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134085

Y. Wang, M. F. Shen, C. , and S. , Essential roles for Pot1b in HSC self-renewal and survival, Blood, vol.118, issue.23, pp.6068-6077, 2011.
DOI : 10.1182/blood-2011-06-361527

F. Zhong, S. A. Savage, M. Shkreli, N. Giri, L. Jessop et al., Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita, Genes & Development, vol.25, issue.1, pp.11-16, 2011.
DOI : 10.1101/gad.2006411
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012932