Yeast Genetics and Molecular Biology 1998
College Park, Maryland
August 1998


Name: Smith, Jeffrey
Mailing Address: Molecular Biology and Genetics, Johns Hopkins University (SOM), 725 N. Wolfe St., Baltimore, MD 21205, USA
Email Address: smith@welchlink.welch.jhu.edu
Phone and Fax numbers: 410-955-2474, 410-614-2987

016

Sir4 Regulates the Strength of Yeast rDNA Silencing Through Modulation of Limited Sir2 Protein Pool.


Jeffrey S. Smith , Emerita Caputo, Jef D. Boeke
Molecular Biology and Genetics, Johns Hopkins University (SOM), 725 N. Wolfe St., Baltimore, MD 21205, USA

Pol II-transcribed marker genes integrated within the rDNA of Saccharomyces cerevisiae are repressed by a phenomenon known as 'rDNA silencing'. SIR2 is the only Silent Information Regulator gene required for rDNA silencing, suggesting that it is related to, but different from silencing associated with telomeres and the HM loci. SIR4 deletion paradoxically strengthened rDNA silencing, suggesting SIR4 may be a regulatory gene. We have now further characterized the modulation of rDNA silencing by SIR4 and found that its rDNA effects are mediated through a limiting pool of Sir2p. rDNA silencing was eliminated by SIR4 overexpression, but restored by co-overexpression with SIR2 . Manipulations of SIR4 shown by others to promote cellular longevity and redistribute Sir proteins from telomeres to the nucleolus, strengthened rDNA silencing in our reporter strains. These manipulations include SIR4-42 and overexpression of the extreme C-terminus of Sir4p. Furthermore, mutations in several genes which lengthen telomeres, weaken rDNA silencing. We conclude that SIR4 regulates rDNA silencing strength by modulating the distribution of Sir2p between the rDNA and competing telomeres. To identify non- SIR genes which participate in rDNA silencing, we have performed a genetic screen for mutants which alter the strength of rDNA silencing. The mutants were separated into two groups, loss of rDNA silencing ( lrs ) and increased rDNA silencing ( irs ). Representatives from both groups will be presented.


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