![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on April 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 5, 2001
Revised on December 12, 2001
Accepted on January 4, 2002
1 Department of Biology, Massachusetts Institute of Technology,
Cambridge, MA 02139
2 Department of Biology, Massachusetts Institute of Technology, Building 68-280A, 77 Massachussetts Ave., Cambridge, MA 02139
* Corresponding author. E-mail address: leng{at}mit.edu.
The yeast SIR2 gene and many of its homologues have been identified as NAD+ dependent histone deacetylases. To get a broader view of the relationship between the histone deacetylase activity of Sir2p and its in vivo functions we have mutated 8 highly conserved residues in the core domain of SIR2. These mutations have a range of effects on the ability of Sir2p to deacetylate histones in vitro and to silence genes at the telomeres and HM loci. Interestingly, there is not a direct correlation between the in vitro and in vivo effects in some of these mutations. We also show that the histone deacetylase activity of Sir2p is necessary for the proper localization of the SIR complex to the telomeres.
This article has been cited by other articles:
|
|
 |
|
  P. J. Lynch and L. N. Rusche A Silencer Promotes the Assembly of Silenced Chromatin Independently of Recruitment Mol. Cell. Biol., January 1, 2009; 29(1): 43 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Haldar and R. T. Kamakaka Schizosaccharomyces pombe Hst4 Functions in DNA Damage Response by Regulating Histone H3 K56 Acetylation Eukaryot. Cell, May 1, 2008; 7(5): 800 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Calzari, I. Orlandi, L. Alberghina, and M. Vai The Histone Deubiquitinating Enzyme Ubp10 Is Involved in rDNA Locus Control in Saccharomyces cerevisiae by Affecting Sir2p Association Genetics, December 1, 2006; 174(4): 2249 - 2254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Khan and P. N. Lewis Use of Substrate Analogs and Mutagenesis to Study Substrate Binding and Catalysis in the Sir2 Family of NAD-dependent Protein Deacetylases J. Biol. Chem., April 28, 2006; 281(17): 11702 - 11711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Liszt, E. Ford, M. Kurtev, and L. Guarente Mouse Sir2 Homolog SIRT6 Is a Nuclear ADP-ribosyltransferase J. Biol. Chem., June 3, 2005; 280(22): 21313 - 21320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kaeberlein, T. McDonagh, B. Heltweg, J. Hixon, E. A. Westman, S. D. Caldwell, A. Napper, R. Curtis, P. S. DiStefano, S. Fields, et al. Substrate-specific Activation of Sirtuins by Resveratrol J. Biol. Chem., April 29, 2005; 280(17): 17038 - 17045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Freeman-Cook, E. B. Gomez, E. J. Spedale, J. Marlett, S. L. Forsburg, L. Pillus, and P. Laurenson Conserved Locus-Specific Silencing Functions of Schizosaccharomyces pombe sir2+ Genetics, March 1, 2005; 169(3): 1243 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Tanny, D. S. Kirkpatrick, S. A. Gerber, S. P. Gygi, and D. Moazed Budding Yeast Silencing Complexes and Regulation of Sir2 Activity by Protein-Protein Interactions Mol. Cell. Biol., August 15, 2004; 24(16): 6931 - 6946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Zhao, R. Harshaw, X. Chai, and R. Marmorstein Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD+-dependent Sir2 histone/protein deacetylases PNAS, June 8, 2004; 101(23): 8563 - 8568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gallo, D. L. Smith Jr., and J. S. Smith Nicotinamide Clearance by Pnc1 Directly Regulates Sir2-Mediated Silencing and Longevity Mol. Cell. Biol., February 1, 2004; 24(3): 1301 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-J. Lin, E. Ford, M. Haigis, G. Liszt, and L. Guarente Calorie restriction extends yeast life span by lowering the level of NADH Genes & Dev., January 1, 2004; 18(1): 12 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hirao, J. Posakony, M. Nelson, H. Hruby, M. Jung, J. A. Simon, and A. Bedalov Identification of Selective Inhibitors of NAD+-dependent Deacetylases Using Phenotypic Screens in Yeast J. Biol. Chem., December 26, 2003; 278(52): 52773 - 52782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Bitterman, O. Medvedik, and D. A. Sinclair Longevity Regulation in Saccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin Microbiol. Mol. Biol. Rev., September 1, 2003; 67(3): 376 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huang and D. Moazed Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing Genes & Dev., September 1, 2003; 17(17): 2162 - 2176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Ng, D. N. Ciccone, K. B. Morshead, M. A. Oettinger, and K. Struhl Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegation PNAS, February 18, 2003; 100(4): 1820 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kaeberlein, A. A. Andalis, G. R. Fink, and L. Guarente High Osmolarity Extends Life Span in Saccharomyces cerevisiae by a Mechanism Related to Calorie Restriction Mol. Cell. Biol., November 15, 2002; 22(22): 8056 - 8066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Bitterman, R. M. Anderson, H. Y. Cohen, M. Latorre-Esteves, and D. A. Sinclair Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1 J. Biol. Chem., November 15, 2002; 277(47): 45099 - 45107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Garcia and L. Pillus A Unique Class of Conditional sir2 Mutants Displays Distinct Silencing Defects in Saccharomyces cerevisiae Genetics, October 1, 2002; 162(2): 721 - 736. [Abstract] [Full Text] [PDF]
|
|
