Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Beverley H. Anderson, Paul R. Kasher, Josephine Mayer, Marcin Szynkiewicz, Emma M. Jenkinson, Sanjeev S. Bhaskar, Jill E. Urquhart, Sarah B. Daly, Jonathan E. Dickerson, James O'Sullivan, Elisabeth Oppliger Leibundgut, Joanne Muter, Ghada M H Abdel-Salem, Riyana Babul-Hirji, Peter Baxter, Andrea Berger, Luisa Bonafé, Janice E. Brunstom-Hernandez, Johannes A. Buckard, David ChitayatWui K. Chong, Duccio M. Cordelli, Patrick Ferreira, Joel Fluss, Ewan H. Forrest, Emilio Franzoni, Caterina Garone, Simon R. Hammans, Gunnar Houge, Imelda Hughes, Sebastien Jacquemont, Pierre Yves Jeannet, Rosalind J. Jefferson, Ram Kumar, Georg Kutschke, Staffan Lundberg, Charles M. Loureno, Ramesh Mehta, Sakkubai Naidu, Ken K. Nischal, Luís Nunes, Katrin Ounap, Michel Philippart, Prab Prabhakar, Sarah R. Risen, Raphael Schiffmann, Calvin Soh, John B P Stephenson, Helen Stewart, Jon Stone, John L. Tolmie, Marjo S. Van Der Knaap, Jose P. Vieira, Catheline N. Vilain, Emma L. Wakeling, Vanessa Wermenbol, Andrea Whitney, Simon C. Lovell, Stefan Meyer, John H. Livingston, Gabriela M. Baerlocher, Graeme C M Black, Gillian I. Rice, J. Yanick

Research output: Contribution to journalArticle

Abstract

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γ 3H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the I ±-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

Original languageEnglish (US)
Pages (from-to)338-342
Number of pages5
JournalNature Genetics
Volume44
Issue number3
DOIs
StatePublished - Mar 2012

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Telomere Shortening
Telomere
Dyskeratosis Congenita
Maintenance
Mutation
Eukaryotic Cells
DNA-Directed DNA Polymerase
DNA Replication
Arabidopsis
Gastrointestinal Tract
Yeasts
Observation
Bone and Bones
Cell Line
DNA
Brain
Enzymes

ASJC Scopus subject areas

  • Genetics

Cite this

Anderson, B. H., Kasher, P. R., Mayer, J., Szynkiewicz, M., Jenkinson, E. M., Bhaskar, S. S., ... Yanick, J. (2012). Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nature Genetics, 44(3), 338-342. https://doi.org/10.1038/ng.1084

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. / Anderson, Beverley H.; Kasher, Paul R.; Mayer, Josephine; Szynkiewicz, Marcin; Jenkinson, Emma M.; Bhaskar, Sanjeev S.; Urquhart, Jill E.; Daly, Sarah B.; Dickerson, Jonathan E.; O'Sullivan, James; Leibundgut, Elisabeth Oppliger; Muter, Joanne; Abdel-Salem, Ghada M H; Babul-Hirji, Riyana; Baxter, Peter; Berger, Andrea; Bonafé, Luisa; Brunstom-Hernandez, Janice E.; Buckard, Johannes A.; Chitayat, David; Chong, Wui K.; Cordelli, Duccio M.; Ferreira, Patrick; Fluss, Joel; Forrest, Ewan H.; Franzoni, Emilio; Garone, Caterina; Hammans, Simon R.; Houge, Gunnar; Hughes, Imelda; Jacquemont, Sebastien; Jeannet, Pierre Yves; Jefferson, Rosalind J.; Kumar, Ram; Kutschke, Georg; Lundberg, Staffan; Loureno, Charles M.; Mehta, Ramesh; Naidu, Sakkubai; Nischal, Ken K.; Nunes, Luís; Ounap, Katrin; Philippart, Michel; Prabhakar, Prab; Risen, Sarah R.; Schiffmann, Raphael; Soh, Calvin; Stephenson, John B P; Stewart, Helen; Stone, Jon; Tolmie, John L.; Van Der Knaap, Marjo S.; Vieira, Jose P.; Vilain, Catheline N.; Wakeling, Emma L.; Wermenbol, Vanessa; Whitney, Andrea; Lovell, Simon C.; Meyer, Stefan; Livingston, John H.; Baerlocher, Gabriela M.; Black, Graeme C M; Rice, Gillian I.; Yanick, J.

In: Nature Genetics, Vol. 44, No. 3, 03.2012, p. 338-342.

Research output: Contribution to journalArticle

Anderson, BH, Kasher, PR, Mayer, J, Szynkiewicz, M, Jenkinson, EM, Bhaskar, SS, Urquhart, JE, Daly, SB, Dickerson, JE, O'Sullivan, J, Leibundgut, EO, Muter, J, Abdel-Salem, GMH, Babul-Hirji, R, Baxter, P, Berger, A, Bonafé, L, Brunstom-Hernandez, JE, Buckard, JA, Chitayat, D, Chong, WK, Cordelli, DM, Ferreira, P, Fluss, J, Forrest, EH, Franzoni, E, Garone, C, Hammans, SR, Houge, G, Hughes, I, Jacquemont, S, Jeannet, PY, Jefferson, RJ, Kumar, R, Kutschke, G, Lundberg, S, Loureno, CM, Mehta, R, Naidu, S, Nischal, KK, Nunes, L, Ounap, K, Philippart, M, Prabhakar, P, Risen, SR, Schiffmann, R, Soh, C, Stephenson, JBP, Stewart, H, Stone, J, Tolmie, JL, Van Der Knaap, MS, Vieira, JP, Vilain, CN, Wakeling, EL, Wermenbol, V, Whitney, A, Lovell, SC, Meyer, S, Livingston, JH, Baerlocher, GM, Black, GCM, Rice, GI & Yanick, J 2012, 'Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus', Nature Genetics, vol. 44, no. 3, pp. 338-342. https://doi.org/10.1038/ng.1084
Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM, Bhaskar SS et al. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nature Genetics. 2012 Mar;44(3):338-342. https://doi.org/10.1038/ng.1084
Anderson, Beverley H. ; Kasher, Paul R. ; Mayer, Josephine ; Szynkiewicz, Marcin ; Jenkinson, Emma M. ; Bhaskar, Sanjeev S. ; Urquhart, Jill E. ; Daly, Sarah B. ; Dickerson, Jonathan E. ; O'Sullivan, James ; Leibundgut, Elisabeth Oppliger ; Muter, Joanne ; Abdel-Salem, Ghada M H ; Babul-Hirji, Riyana ; Baxter, Peter ; Berger, Andrea ; Bonafé, Luisa ; Brunstom-Hernandez, Janice E. ; Buckard, Johannes A. ; Chitayat, David ; Chong, Wui K. ; Cordelli, Duccio M. ; Ferreira, Patrick ; Fluss, Joel ; Forrest, Ewan H. ; Franzoni, Emilio ; Garone, Caterina ; Hammans, Simon R. ; Houge, Gunnar ; Hughes, Imelda ; Jacquemont, Sebastien ; Jeannet, Pierre Yves ; Jefferson, Rosalind J. ; Kumar, Ram ; Kutschke, Georg ; Lundberg, Staffan ; Loureno, Charles M. ; Mehta, Ramesh ; Naidu, Sakkubai ; Nischal, Ken K. ; Nunes, Luís ; Ounap, Katrin ; Philippart, Michel ; Prabhakar, Prab ; Risen, Sarah R. ; Schiffmann, Raphael ; Soh, Calvin ; Stephenson, John B P ; Stewart, Helen ; Stone, Jon ; Tolmie, John L. ; Van Der Knaap, Marjo S. ; Vieira, Jose P. ; Vilain, Catheline N. ; Wakeling, Emma L. ; Wermenbol, Vanessa ; Whitney, Andrea ; Lovell, Simon C. ; Meyer, Stefan ; Livingston, John H. ; Baerlocher, Gabriela M. ; Black, Graeme C M ; Rice, Gillian I. ; Yanick, J. / Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. In: Nature Genetics. 2012 ; Vol. 44, No. 3. pp. 338-342.
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