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

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
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 ?H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the ?-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-? primase, 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.

1061-4036
338-342
Anderson, Beverley H
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Kasher, Paul R
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Jenkinson, Emma M
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Urquhart, Jill E
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Daly, Sarah B
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Dickerson, Jonathan E
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O'Sullivan, James
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Leibundgut, Elisabeth Oppliger
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Muter, Joanne
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Babul-Hirji, Riyana
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Buckard, Johannes A
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Fluss, Joel
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Mehta, Ramesh
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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, Lourenço, Charles M, Mehta, Ramesh, Naidu, Sakkubai, Nischal, Ken K, Nunes, Luís, Õunap, 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 and Crow, Yanick J (2012) Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nature Genetics, 44 (3), 338-342. (doi:10.1038/ng.1084).

Record type: Article

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 ?H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the ?-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-? primase, 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.

Full text not available from this repository.

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Published date: 22 January 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 334296
URI: https://eprints.soton.ac.uk/id/eprint/334296
ISSN: 1061-4036
PURE UUID: ab6bbe3b-da47-40c5-982e-ade7156eebed

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Date deposited: 06 Mar 2012 15:32
Last modified: 25 Sep 2019 16:32

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Contributors

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

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