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

Anderson, B.H. et al. (2012) Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nature Genetics, 44(3), pp. 338-342. (doi: 10.1038/ng.1084) (PMID:22267198)

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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 γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stephenson, Prof John and Forrest, Dr Ewan and Dickerson, Dr Jonathan
Authors: Anderson, B.H., Kasher, P.R., Mayer, J., Szynkiewicz, M., Jenkinson, E.M., Bhaskar, S.S., Urquhart, J.E., Daly, S.B., Dickerson, J.E., O'Sullivan, J., Leibundgut, E.O., Muter, J., Abdel-Salem, G.M.H., Babul-Hirji, R., Baxter, P., Berger, A., Bonafé, L., Brunstom-Hernandez, J.E., Buckard, J.A., Chitayat, D., Chong, W.K., Cordelli, D.M., Ferreira, P., Fluss, J., Forrest, E., Franzoni, E., Garone, C., Hammans, S.R., Houge, G., Hughes, I., Jacquemont, S., Jeannet, P., Jefferson, R.J., Kumar, R., Kutschke, G., Lundberg, S., Lourenço, C.M., Mehta, R., Naidu, S., Nischal, K.K., Nunes, L., Õunap, K., Philippart, M., Prabhakar, P., Risen, S.R., Schiffmann, R., Soh, C., Stephenson, J., Stewart, H., Stone, J., Tolmie, J., van der Knaap, M.S., Vieira, J.P., Vilain, C.N., Wakeling, E.L., Wermenbol, V., Whitney, A., Lovell, S.C., Meyer, S., Livingston, J.H., Baerlocher, G.M., Black, G.C.M., Rice, G.I., and Crow, Y.J.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Nature Genetics
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:22 January 2012

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