The long-term objective is to understand the eukaryotic nucleus, using the yeast, Saccharomyces cerevisiae, as a model system. The overall aim is to identify genes affecting structure and function in the nucleus. Current effort is focused in three areas. 1) the mechanism of transcriptional silencing of the mating type loci and telomeres. This silencing is thought to be due to the yeast equivalent of heterochromatin. A novel genetic screen has identified a number of new genes that appear to play a role in silencing. The functions of these genes will be investigated. One of the genes encodes a protein that binds to SIR4; the possibility that this binding is responsible for bringing silent chromatin to the nuclear periphery will be tested. 2) a study of the evolutionarily conserved gene, ASF1. The function of this protein in the nucleus is unknown. It may play a role in repair of DNA damage in chromatin. The two-hybrid system, genetic screens and biochemical methods will be used to find proteins that interact with ASF1. 3) a study of an essential gene, HBP3, and its possible role in chromatin remodeling or histone deposition during DNA replication. 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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Carter, Anthony D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
State University New York Stony Brook
Schools of Arts and Sciences
Stony Brook
United States
Zip Code
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