Related Experiment Video
Updated: Jun 1, 2026

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
Published on: November 25, 2022
Alpha-synuclein functions in the nucleus to protect against hydroxyurea-induced replication stress in yeast
Xianpeng Liu1, Yong Joo Lee, Liang-Chun Liou
1Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Abstract:
Hydroxyurea (HU) inhibits ribonucleotide reductase (RNR), which catalyzes the rate-limiting synthesis of deoxyribonucleotides for DNA replication. HU is used to treat HIV, sickle-cell anemia and some cancers. We found that, compared with vector control cells, low levels of alpha-synuclein (α-syn) protect S. cerevisiae cells from the growth inhibition and reactive oxygen species (ROS) accumulation induced by HU. Analysis of this effect using different α-syn mutants revealed that the α-syn protein functions in the nucleus and not the cytoplasm to modulate S-phase checkpoint responses: α-syn up-regulates histone acetylation and RNR levels, maintains helicase minichromosome maintenance protein complexes (Mcm2-7) on chromatin and inhibits HU-induced ROS accumulation. Strikingly, when residues 2-10 or 96-140 are deleted, this protective function of α-syn in the nucleus is abolished. Understanding the mechanism by which α-syn protects against HU could expand our knowledge of the normal function of this neuronal protein.
Related Concept Videos
Additional Subnuclear Structures
The nucleus contains many membrane-less subnuclear organelles or nuclear bodies, such as nucleoli, Cajal bodies, speckles, paraspeckles, etc. These nuclear...
Regulation of Nuclear Protein Sorting
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Nucleoid
Replication in Eukaryotes
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...

