Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3.
Positioning of telomeres at the nuclear periphery can have dramatic effects on gene expression by establishment of heritable, transcriptionally repressive subdomains. However, little is known about the integral membrane proteins that mediate telomere tethering at the nuclear envelope. Here, we find a previously unrecognized function for the Saccharomyces cerevisiae Sad1-UNC-84 domain protein Mps3 in regulating telomere positioning in mitotic cells. Our data demonstrate that the nucleoplasmic N-terminal acidic domain of Mps3 is not essential for viability. However, this acidic domain is necessary and sufficient for telomere tethering during S phase and the silencing of reporter constructs integrated at telomeres. We show that this is caused by the role of the Mps3 acidic domain in binding and localization of the silent information regulator protein Sir4 to the nuclear periphery. Thus, Mps3 functions as an integral membrane anchor for telomeres and is a novel nuclear receptor for the Sir4 pathway of telomere tethering and gene inactivation.
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Jennifer M
JM
Bupp
Adriana E
AE
Martin
Elizabeth S
ES
Stensrud
Sue L
SL
Jaspersen
D018797:Cell Cycle Proteins / Q000737:chemistry*; D002467:Cell Nucleus / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D015825:Chromosomes, Fungal / Q000378:metabolism; D020868:Gene Silencing; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016196:S Phase; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D004718:Saccharomycetales / Q000166:cytology* / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C471174:Mps3 protein, S cerevisiae; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C061573:SIR4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae