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- Title
The Anaphase Promoting Complex Regulates Yeast Lifespan and rDNA Stability by Targeting Fob1 for Degradation.
- Authors
Menzel, Johannes; Malo, Mackenzie E.; Chan, Cynthia; Prusinkiewicz, Martin; Arnason, Terra G.; Harkness, Troy A. A.
- Abstract
Genomic stability, stress response, and nutrient signaling all play critical, evolutionarily conserved roles in lifespan determination. However, the molecular mechanisms coordinating these processes with longevity remain unresolved. Here we investigate the involvement of the yeast anaphase promoting complex (APC) in longevity. The APC governs passage through M and G1 via ubiquitin-dependent targeting of substrate proteins and is associated with cancer and premature aging when defective. Our twohybrid screen utilizing Apc5 as bait recovered the lifespan determinant Fob1 as prey. Fob1 is unstable specifically in G1, cycles throughout the cell cycle in a manner similar to Clb2 (an APC target), and is stabilized in APC (apc5CA) and proteasome (rpn10Δ) mutants. Deletion of FOB1 increased replicative lifespan (RLS) in wild type (WT), apc5CA, and apc10Δ cells, and suppressed apc5CA cell cycle progression and rDNA recombination defects. Alternatively, increased FOB1 expression decreased RLS in WT cells, but did not reduce the already short apc5CA RLS, suggesting an epistatic interaction between apc5CA and fob1Δ. Mutation to a putative L-Box (Fob1E420V), a Destruction Box-like motif, abolished Fob1 modifications, stabilized the protein, and increased rDNA recombination. Our work provides a mechanistic role played by the APC to promote replicative longevity and genomic stability in yeast.
- Subjects
GENOMICS; YEAST research; DNA replication; PREMATURE aging (Medicine); PROTEIN analysis
- Publication
Genetics, 2014, Vol 196, Issue 3, p693
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1534/genetics.113.158949