Skip Navigation


Nucleic Acids Research Advance Access originally published online on August 5, 2009
Nucleic Acids Research 2009 37(18):6105-6115; doi:10.1093/nar/gkp636
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (2147K) Freely available
Right arrow Screen PDF (731K) Freely available
Right arrowOA All Versions of this Article:
37/18/6105    most recent
gkp636v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Ting, N. S. Y.
Right arrow Articles by Beattie, T. L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ting, N. S. Y.
Right arrow Articles by Beattie, T. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2009, Vol. 37, No. 18 6105-6115
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

The human telomerase RNA component, hTR, activates the DNA-dependent protein kinase to phosphorylate heterogeneous nuclear ribonucleoprotein A1

Nicholas S. Y. Ting1, Brant Pohorelic1, Yaping Yu1, Susan P. Lees-Miller1,2 and Tara L. Beattie1,2,*

1Department of Biochemistry and Molecular Biology and 2Department of Oncology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive N.W. Calgary, AB, Canada T2N 4N1

*To whom correspondence should be addressed. Tel: +1 403 220 8328; Fax: +1 403 283 8727; Email: tbeattie{at}ucalgary.ca

Received September 5, 2008. Revised July 10, 2009. Accepted July 15, 2009.

Telomere integrity in human cells is maintained by the dynamic interplay between telomerase, telomere associated proteins, and DNA repair proteins. These interactions are vital to suppress DNA damage responses and unfavorable changes in chromosome dynamics. The DNA-dependent protein kinase (DNA-PK) is critical for this process. Cells deficient for functional DNA-PKcs show increased rates of telomere loss, accompanied by chromosomal fusions and translocations. Treatment of cells with specific DNA-PK kinase inhibitors leads to similar phenotypes. These observations indicate that the kinase activity of DNA-PK is required for its function at telomeres possibly through phosphorylation of essential proteins needed for telomere length maintenance. Here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a direct substrate for DNA-PK in vitro. Phosphorylation of hnRNP A1 is stimulated not only by the presence of DNA but also by the telomerase RNA component, hTR. Furthermore, we show that hnRNP A1 is phosphorylated in vivo in a DNA-PK-dependent manner and that this phosphorylation is greatly reduced in cell lines which lack hTR. These data are the first to report that hTR stimulates the kinase activity of DNA-PK toward a known telomere-associated protein, and may provide further insights into the function of DNA-PK at telomeres.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.