title: Yeast Tdh3 (glyceraldehyde 3-phosphate dehydrogenase) is a Sir2-interacting factor that regulates transcriptional silencing and rDNA recombination.
abstract: Sir2 is an NAD(+)-dependent histone deacetylase required to mediate transcriptional silencing and suppress rDNA recombination in budding yeast. We previously identified Tdh3, a glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as a high expression suppressor of the lethality caused by Sir2 overexpression in yeast cells. Here we show that Tdh3 interacts with Sir2, localizes to silent chromatin in a Sir2-dependent manner, and promotes normal silencing at the telomere and rDNA. Characterization of specific TDH3 alleles suggests that Tdh3's influence on silencing requires nuclear localization but does not correlate with its catalytic activity. Interestingly, a genetic assay suggests that Tdh3, an NAD(+)-binding protein, influences nuclear NAD(+) levels; we speculate that Tdh3 links nuclear Sir2 with NAD(+) from the cytoplasm.
authors.affiliation: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut, United States of America.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Ringel
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ryznar
authors.forename: Hannah
authors.initials: H
authors.lastname: Picariello
authors.forename: Kuan-lin
authors.initials: KL
authors.lastname: Huang
authors.forename: Asmitha G
authors.initials: AG
authors.lastname: Lazarus
authors.forename: Scott G
authors.initials: SG
authors.lastname: Holmes
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D060066:Protein Interaction Maps / Q000235:genetics; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004275:DNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D009243:NAD; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C465226:TDH3 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2