This grant application is for the continuation of genetic studies of silencing in Soccharomyces cerevisiae, a project entering its 17th year. Accomplishments in the most recent renewal period include 1)establishment that ORC is the replication initiator in yeast, 2) discovery that the silencing and replication functions of ORC are separable, 3) establishing that replication initiation from the silencer is not required for silencing, 4) discovery that ORC bound to silencers recruits Sirlp to the silencer throughbinding to a specific set of amino acids in Skip, 5) discovery that at least some functions of ORC are conserved between yeast and Drosophila, 6) discovery of a presumptive acetyltransferaseinvolved hi silencer function, possibly through affects on ORC or origins, 7) discovery of five new proteins involved in silencing, two of which have human homologs with direct connection to leukemia. 8) discovery that Drosophila Sir2 protein is a regulator of position effects. 9) discovery of a potential M phase role for ORC 10)discovery of the first chromatin boundary element in yeast. 11) discovery of silencing proteins in K. lactis that challenge existing models for telomere length regulation, and several more discoveries. Two technical breakthroughsincludethe ability to visualize ORC on meiotic and mitotic chromosomes, and antibody localization of Drosophila Sir2p. In the coming period, the project will 1) determine if replication throughHMRis required to establish silencing, 2) test whether ore mutants' M-phase arrest reflects a new check point or a role for ORC in promoting sister chromatid segregation, 3) use the ability to visualize ORC on metaphase chromosomes to answerfundamental questions about ORC vis-a -vis replication and silencing, 4) determine the role of newly discovered ORC binding proteins, 5) identify new conditional ORC mutations for ordering events in the cell cycle, 6) figure out how SUM1-1 mediates silencing, 7) learn how chromatin boundary elements are assembled and function, 8) test for other silenced regions in the genome, 9) determine how a presumptive protein methyltransferaseaffects silencing, and 10)resolve the basis of the different silencing properties of artificial and natural telomeres.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Carter, Anthony D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
Schools of Arts and Sciences
United States
Zip Code
Sieverman, Kathryn J; Rine, Jasper (2018) Impact of Homologous Recombination on Silent Chromatin in Saccharomyces cerevisiae. Genetics 208:1099-1113
McCleary, David F; Rine, Jasper (2017) Nutritional Control of Chronological Aging and Heterochromatin in Saccharomyces cerevisiae. Genetics 205:1179-1193
Schlissel, Gavin; Krzyzanowski, Marek K; Caudron, Fabrice et al. (2017) Aggregation of the Whi3 protein, not loss of heterochromatin, causes sterility in old yeast cells. Science 355:1184-1187
Dodson, Anne E; Rine, Jasper (2016) Donor Preference Meets Heterochromatin: Moonlighting Activities of a Recombinational Enhancer in Saccharomyces cerevisiae. Genetics 204:1065-1074
Ellahi, Aisha; Rine, Jasper (2016) Evolution and Functional Trajectory of Sir1 in Gene Silencing. Mol Cell Biol 36:1164-79
McCleary, David F; Steakley, David Lee; Rine, Jasper (2016) Sir protein-independent repair of dicentric chromosomes in Saccharomyces cerevisiae. Mol Biol Cell 27:2879-83
Liu, Tzu-Yu; Dodson, Anne E; Terhorst, Jonathan et al. (2016) Riches of phenotype computationally extracted from microbial colonies. Proc Natl Acad Sci U S A 113:E2822-31
Steakley, David Lee; Rine, Jasper (2015) On the Mechanism of Gene Silencing in Saccharomyces cerevisiae. G3 (Bethesda) 5:1751-63
Lombardi, Laura M; Davis, Matthew D; Rine, Jasper (2015) Maintenance of nucleosomal balance in cis by conserved AAA-ATPase Yta7. Genetics 199:105-16
Dodson, Anne E; Rine, Jasper (2015) Heritable capture of heterochromatin dynamics in Saccharomyces cerevisiae. Elife 4:e05007

Showing the most recent 10 out of 88 publications