Nucleic Acids Research Advance Access originally published online on December 23, 2007
Nucleic Acids Research 2008 36(4):1200-1208; doi:10.1093/nar/gkm1137
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2008, Vol. 36, No. 4 1200-1208
© 2007 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.
Structural Biology |
G-quadruplex preferentially forms at the very 3' end of vertebrate telomeric DNA
1Laboratory of Biochemistry and Biophysics, College of Life Sciences, Wuhan University, Wuhan 430072 and 2State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China
*To whom correspondence should be addressed: Tel: +86 10 6480 7259, Fax: +86 10 6480 7099; Email: z.tan{at}ioz.ac.cn or tanclswu{at}public.wh.hb.cn
Received October 21, 2007. Revised November 16, 2007. Accepted December 6, 2007.
Human chromosome ends are protected with kilobases repeats of TTAGGG. Telomere DNA shortens at replication. This shortening in most tumor cells is compensated by telomerase that adds telomere repeats to the 3' end of the G-rich telomere strand. Four TTAGGG repeats can fold into G-quadruplex that is a poor substrate for telomerase. This property has been suggested to regulate telomerase activity in vivo and telomerase inhibition via G-quadruplex stabilization is considered a therapeutic strategy against cancer. Theoretically G-quadruplex can form anywhere along the long G-rich strand. Where G-quadruplex forms determines whether the 3' telomere end is accessible to telomerase and may have implications in other functions telomere plays. We investigated G-quadruplex formation at different positions by DMS footprinting and exonuclease hydrolysis. We show that G-quadruplex preferentially forms at the very 3' end than at internal positions. This property provides a molecular basis for telomerase inhibition by G-quadruplex formation. Moreover, it may also regulate those processes that depend on the structure of the very 3' telomere end, for instance, the alternative lengthening of telomere mechanism, telomere T-loop formation, telomere end protection and the replication of bulky telomere DNA. Therefore, targeting telomere G-quadruplex may influence more telomere functions than simply inhibiting telomerase.
Present Address: Zhong-yuan Kan, Department of Biochemistry and Biophysics, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104, USA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. A. Cahoon and H. S. Seifert An Alternative DNA Structure Is Necessary for Pilin Antigenic Variation in Neisseria gonorrhoeae Science, August 7, 2009; 325(5941): 764 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Lee and D. S. Kim Dramatic effect of single-base mutation on the conformational dynamics of human telomeric G-quadruplex Nucleic Acids Res., June 1, 2009; 37(11): 3625 - 3634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Lane, J. B. Chaires, R. D. Gray, and J. O. Trent Stability and kinetics of G-quadruplex structures Nucleic Acids Res., October 1, 2008; 36(17): 5482 - 5515. [Abstract] [Full Text] [PDF]
|
|