Abstract

The long term objective is to understand the eukaryotic nucleus, using the yeast, Saccharomyces cerevisiae, as a model system. The goal is to identify and characterize genes affecting the structure and function of chromosomes. Current effort is focused on understanding the mechanism of transcriptional silencing of the yeast silent mating-type loci and telomeres. These silenced chromosomal domains are the yeast equivalent of heterochromatin in metazoans. The roles of Sir3 and Sir4 proteins in silencing will be studied in detail. Specifically, the role of the Sir3 N-terminal BAH domain and a conserved domain of Sir4 will be investigated. The possible role of acetyl ADP-ribose as a signalling molecule in silencing will be examined. The possible sumoylation of Sir4 will also be studied. Another aim will be to search for a histone demethylase gene. Recent work has shown that methylation of specific lysine residues of histones H3 and H4 is very important for gene regulation. There is some evidence that this modification is reversible but no lysine demethylase gene or enzyme has been identified. Various biochemical and genetic approaches will be undertaken to find such a gene. Progress in these areas will shed light on chromosome structure and function in the eukaryotic nucleus, not only in yeast but also in mammalian cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028220-26
Application #
6905609
Study Section
Special Emphasis Panel (ZRG1-MBC-2 (01))
Program Officer
Carter, Anthony D
Project Start
1980-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
26
Fiscal Year
2005
Total Cost
$368,725
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Biochemistry
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Hsu, Hao-Chi; Wang, Chia-Lin; Wang, Mingzhu et al. (2013) Structural basis for allosteric stimulation of Sir2 activity by Sir4 binding. Genes Dev 27:64-73
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
Sampath, Vinaya; Yuan, Peihua; Wang, Isabel X et al. (2009) Mutational analysis of the Sir3 BAH domain reveals multiple points of interaction with nucleosomes. Mol Cell Biol 29:2532-45
Krichevsky, Alexander; Gutgarts, Helen; Kozlovsky, Stanislav V et al. (2007) C2H2 zinc finger-SET histone methyltransferase is a plant-specific chromatin modifier. Dev Biol 303:259-69
Vaquero, Alejandro; Scher, Michael B; Lee, Dong Hoon et al. (2006) SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev 20:1256-61
Connelly, Jessica J; Yuan, Peihua; Hsu, Hao-Chi et al. (2006) Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain. Mol Cell Biol 26:3256-65
Zappulla, David C; Maharaj, Arindel S R; Connelly, Jessica J et al. (2006) Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs. BMC Mol Biol 7:40
Xiang, Song; Kim, Eun Young; Connelly, Jessica J et al. (2006) The crystal structure of Cdc42 in complex with collybistin II, a gephyrin-interacting guanine nucleotide exchange factor. J Mol Biol 359:35-46
Liu, Bingsheng; Sutton, Ann; Sternglanz, Rolf (2005) A yeast polyamine acetyltransferase. J Biol Chem 280:16659-64
Wang, Xiaorong; Connelly, Jessica J; Wang, Chia-Lin et al. (2004) Importance of the Sir3 N terminus and its acetylation for yeast transcriptional silencing. Genetics 168:547-51

Showing the most recent 10 out of 35 publications