| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Protein Has No Effect on Global Gene Silencing in Mouse Embryonic Stem Cells1
1 Ottawa Regional Cancer Centre and 2 University of Ottawa, Ottawa, Canada; and
3 Northwestern Regional Cancer Centre, Thunder Bay, Canada
Requests for reprints: Michael W. McBurney, Ottawa Regional Cancer Centre, 503 Smyth Road, Ottawa, K1H 1C4 Canada. Phone: (613) 737-7700x6887; Fax: (613) 247-3524. E-mail: michael.mcburney{at}orcc.on.ca
The yeast sir2 gene plays a central role in mediating gene silencing and DNA repair in this organism. The mouse sir2
gene is closely related to its yeast homologue and encodes a nuclear protein expressed at particularly high levels in embryonic stem (ES) cells. We used homologous recombination to create ES cells null for sir2 and found that these cells did not have elevated levels of acetylated histones and did not ectopically express silent genes. Unlike yeast sir2 mutants, our sir2 null ES cells had normal sensitivity to insults such as ionizing radiation and heat shock, and they were able to silence invading retroviruses normally. These sir2 null cells were able to differentiate in culture normally. Our results failed to provide evidence that the mammalian SIR2 protein plays a role in gene silencing and suggest that the physiological substrate(s) for the SIR2 deacetylase may be nuclear proteins other than histones.
Key Words: targeted recombination • gene inactivation • retrovirus • embryonic stem cell
This article has been cited by other articles:
|
|
 |
|
  S. A. Gatz and L. Wiesmuller Take a break--resveratrol in action on DNA Carcinogenesis, February 1, 2008; 29(2): 321 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Solomon, R. Pasupuleti, L. Xu, T. McDonagh, R. Curtis, P. S. DiStefano, and L. J. Huber Inhibition of SIRT1 Catalytic Activity Increases p53 Acetylation but Does Not Alter Cell Survival following DNA Damage Mol. Cell. Biol., January 1, 2006; 26(1): 28 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Michishita, J. Y. Park, J. M. Burneskis, J. C. Barrett, and I. Horikawa Evolutionarily Conserved and Nonconserved Cellular Localizations and Functions of Human SIRT Proteins Mol. Biol. Cell, October 1, 2005; 16(10): 4623 - 4635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Matsushita, Y. Takami, M. Kimura, S. Tachiiri, M. Ishiai, T. Nakayama, and M. Takata Role of NAD-dependent deacetylases SIRT1 and SIRT2 in radiation and cisplatin-induced cell death in vertebrate cells Genes Cells, April 1, 2005; 10(4): 321 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sereno, A. M. Alegre, R. Silvestre, B. Vergnes, and A. Ouaissi In Vitro Antileishmanial Activity of Nicotinamide Antimicrob. Agents Chemother., February 1, 2005; 49(2): 808 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Daitoku, M. Hatta, H. Matsuzaki, S. Aratani, T. Ohshima, M. Miyagishi, T. Nakajima, and A. Fukamizu Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity PNAS, July 6, 2004; 101(27): 10042 - 10047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Buck, C. M. Gallo, and J. S. Smith Diversity in the Sir2 family of protein deacetylases J. Leukoc. Biol., June 1, 2004; 75(6): 939 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-L. Cheng, R. Mostoslavsky, S.'i. Saito, J. P. Manis, Y. Gu, P. Patel, R. Bronson, E. Appella, F. W. Alt, and K. F. Chua Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice PNAS, September 16, 2003; 100(19): 10794 - 10799. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
