Skip Navigation


Nucleic Acids Research Advance Access originally published online on September 13, 2006
Nucleic Acids Research 2006 34(17):4791-4800; doi:10.1093/nar/gkl645
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (4775K) Freely available
Right arrow Screen PDF (718K) Freely available
Right arrowOA All Versions of this Article:
34/17/4791    most recent
gkl645v1
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 ISI Web of Science
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 Search for citing articles in:
ISI Web of Science (11)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Rosen, L. E.
Right arrow Articles by Seligman, L. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rosen, L. E.
Right arrow Articles by Seligman, L. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2006, Vol. 34, No. 17 4791-4800
© 2006 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.

Nucleic Acid Enzymes

Homing endonuclease I-CreI derivatives with novel DNA target specificities

Laura E. Rosen1,2, Holly A. Morrison1, Selma Masri1, Michael J. Brown1, Brendan Springstubb1, Django Sussman2, Barry L. Stoddard2 and Lenny M. Seligman1,*

1 Department of Biology and Program in Molecular Biology, Pomona College 175 West 6th Street, Claremont, CA 91711, USA 2 Division of Basic Sciences, Fred Hutchinson Cancer Research Center 1100 Fairview Avenue North A3-025 Seattle, WA 98109, USA

*To whom correspondence should be addressed. Tel: +1 909 621 8608; Fax: +1 909 621 8878; Email: lms14747{at}pomona.edu

Received June 9, 2006. Accepted August 21, 2006.

Homing endonucleases are highly specific enzymes, capable of recognizing and cleaving unique DNA sequences in complex genomes. Since such DNA cleavage events can result in targeted allele-inactivation and/or allele-replacement in vivo, the ability to engineer homing endonucleases matched to specific DNA sequences of interest would enable powerful and precise genome manipulations. We have taken a step-wise genetic approach in analyzing individual homing endonuclease I-CreI protein/DNA contacts, and describe here novel interactions at four distinct target site positions. Crystal structures of two mutant endonucleases reveal the molecular interactions responsible for their altered DNA target specificities. We also combine novel contacts to create an endonuclease with the predicted target specificity. These studies provide important insights into engineering homing endonucleases with novel target specificities, as well as into the evolution of DNA recognition by this fascinating family of proteins.

Present addresses: Holly A. Morrison, Department of Molecular and Cell Biology, UC Berkeley, Berkeley, CA 94720, USA

Selma Masri, Department of Surgical Research, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA


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


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Yahara, M. Fukuyo, A. Sasaki, and I. Kobayashi
Evolutionary maintenance of selfish homing endonuclease genes in the absence of horizontal transfer
PNAS, November 3, 2009; 106(44): 18861 - 18866.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Jarjour, H. West-Foyle, M. T. Certo, C. G. Hubert, L. Doyle, M. M. Getz, B. L. Stoddard, and A. M. Scharenberg
High-resolution profiling of homing endonuclease binding and catalytic specificity using yeast surface display
Nucleic Acids Res., November 1, 2009; 37(20): 6871 - 6880.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Grizot, J. Smith, F. Daboussi, J. Prieto, P. Redondo, N. Merino, M. Villate, S. Thomas, L. Lemaire, G. Montoya, et al.
Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease
Nucleic Acids Res., September 1, 2009; 37(16): 5405 - 5419.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. M. Lippow, P. M. Aha, M. H. Parker, W. J. Blake, B. M. Baynes, and D. Lipovsek
Creation of a type IIS restriction endonuclease with a long recognition sequence
Nucleic Acids Res., May 1, 2009; 37(9): 3061 - 3073.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
H. Li, S. Pellenz, U. Ulge, B. L. Stoddard, and R. J. Monnat Jr
Generation of single-chain LAGLIDADG homing endonucleases from native homodimeric precursor proteins
Nucleic Acids Res., April 1, 2009; 37(5): 1650 - 1662.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
Z. Chen, F. Wen, N. Sun, and H. Zhao
Directed evolution of homing endonuclease I-SceI with altered sequence specificity
Protein Eng. Des. Sel., April 1, 2009; 22(4): 249 - 256.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. H. Eastberg, A. M. Smith, L. Zhao, J. Ashworth, B. W. Shen, and B. L. Stoddard
Thermodynamics of DNA target site recognition by homing endonucleases
Nucleic Acids Res., December 18, 2007; 35(21): 7209 - 7221.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
N. Windbichler, P. A. Papathanos, F. Catteruccia, H. Ranson, A. Burt, and A. Crisanti
Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos
Nucleic Acids Res., September 27, 2007; 35(17): 5922 - 5933.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Prieto, P. Redondo, D. Padro, S. Arnould, J.-C. Epinat, F. Paques, F. J. Blanco, and G. Montoya
The C-terminal loop of the homing endonuclease I-CreI is essential for site recognition, DNA binding and cleavage
Nucleic Acids Res., May 11, 2007; 35(10): 3262 - 3271.
[Abstract] [Full Text] [PDF]


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.