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Genetics

Title:		Mcm10 is required for the maintenance of transcriptional silencing in Saccharomyces cerevisiae
Author(s):		Liachko I; Tye BK;
Address:		"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA"
Journal Title:		Genetics
Year:		2005
Volume:		20050805
Issue:		2
Page Number:		503 - 515
DOI:		10.1534/genetics.105.042333
ISSN/ISBN:		0016-6731 (Print) 0016-6731 (Linking)
Abstract:		"Mcm10 is an essential protein that participates in both the initiation and the elongation of DNA replication. In this study we demonstrate a role for Mcm10 in the maintenance of heterochromatic silencing at telomeres and HM loci of budding yeast. Two mcm10 mutants drastically reduce silencing of both URA3 and ADE2 reporter genes integrated into these silent loci. When exposed to alpha-factor, mcm10 mutant cells display a 'shmoo-cluster' phenotype associated with a defect in the maintenance of silencing. In addition, when combined with a defect in the establishment of silent chromatin, mcm10 mutants demonstrate a synergistic defect in HML silencing. Consistent with a direct silencing function, Mcm10p shows a two-hybrid interaction with Sir2p and Sir3p that is destroyed by the mcm10-1 mutation and dependent on the C-terminal 108 amino acids. Tethering GBD-MCM10 to a defective HMR-E silencer is not sufficient to restore silencing. Furthermore, mutations in MCM10 inhibit the ability of GBD-SIR3 to restore silencing when tethered to a defective HMR-E. Suppressor mutations in MCM2, which suppress the temperature sensitivity of mcm10-1, fail to overcome the mcm10-1 silencing defect, suggesting that MCM10's role in transcriptional silencing may be separate from its essential functions in DNA replication"
Keywords:		"Cell Cycle Proteins/*genetics/physiology Chromosomal Proteins, Non-Histone Fungal Proteins/metabolism Gene Expression Regulation, Fungal/*genetics Histone Deacetylases/metabolism Mating Factor Minichromosome Maintenance Proteins Mutation/genetics Peptides;"
Notes:		"MedlineLiachko, Ivan Tye, Bik K eng GM34190/GM/NIGMS NIH HHS/ GM7617/GM/NIGMS NIH HHS/ Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2005/08/09 Genetics. 2005 Oct; 171(2):503-15. doi: 10.1534/genetics.105.042333. Epub 2005 Aug 5"