The long term goal of this research is to understand the role of histone acetylation and deacetylation in chromatin structure and function, using the yeast Saccharomyces cerevisiae to study these processes. Since many of the yeast proteins involved in acetylation/deacetylation have human homologs, this project should shed light on human biology and disease.
The specific aims for this period are: 1) to learn about the enzymatic mechanism of Sir2 and related proteins, recently demonstrated to be NAD-dependent protein deacetylases, 2) to determine if the role of Sir2 in transcriptional silencing is histone deacetylation, 3) to determine the in vivo roles of the yeast Sir2 homologs Hst2, Hst3 and Hst4, 4) to understand how the proteins SUM1-1 and Hstl can silence the mating type loci, HML and HMR, in the absence of Sir2, and 5) to demonstrate that the yeast proteins Sas2 and SptlO are acetyltransferases and to determine if their substrates are histones or other proteins,

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM055641-05
Application #
6331573
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Carter, Anthony D
Project Start
1997-05-01
Project End
2005-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
5
Fiscal Year
2001
Total Cost
$283,628
Indirect Cost
Name
State University New York Stony Brook
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Sampath, Vinaya; Liu, Bingsheng; Tafrov, Stefan et al. (2013) Biochemical characterization of Hpa2 and Hpa3, two small closely related acetyltransferases from Saccharomyces cerevisiae. J Biol Chem 288:21506-13
Yuan, Hua; Rossetto, Dorine; Mellert, Hestia et al. (2012) MYST protein acetyltransferase activity requires active site lysine autoacetylation. EMBO J 31:58-70
Yu, Yao; Srinivasan, Madhusudhan; Nakanishi, Shima et al. (2011) A conserved patch near the C terminus of histone H4 is required for genome stability in budding yeast. Mol Cell Biol 31:2311-25
Srinivasan, Madhusudhan; Mehta, Preeti; Yu, Yao et al. (2011) The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A. EMBO J 30:873-81
Ren, Jie; Wang, Chia-Lin; Sternglanz, Rolf (2010) Promoter strength influences the S phase requirement for establishment of silencing at the Saccharomyces cerevisiae silent mating type Loci. Genetics 186:551-60
Yu, Yao; Neiman, Aaron M; Sternglanz, Rolf (2010) The JmjC domain of Gis1 is dispensable for transcriptional activation. FEMS Yeast Res 10:793-801
Kumar, P Rajesh; Yu, Yao; Sternglanz, Rolf et al. (2008) NADP regulates the yeast GAL induction system. Science 319:1090-2
Chu, Yaya; Sutton, Ann; Sternglanz, Rolf et al. (2006) The BUR1 cyclin-dependent protein kinase is required for the normal pattern of histone methylation by SET2. Mol Cell Biol 26:3029-38
Hess, David; Liu, Bingsheng; Roan, Nadia R et al. (2004) Spt10-dependent transcriptional activation in Saccharomyces cerevisiae requires both the Spt10 acetyltransferase domain and Spt21. Mol Cell Biol 24:135-43
Min, J; Landry, J; Sternglanz, R et al. (2001) Crystal structure of a SIR2 homolog-NAD complex. Cell 105:269-79

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