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dc.contributor.authorHua, Sansan
dc.date.accessioned2022-08-29T07:03:01Z
dc.date.available2022-08-29T07:03:01Z
dc.date.issued2022-08-29
dc.identifier.isbn978-91-8009-931-8 (Tryckt)
dc.identifier.isbn978-91-8009-932-5 (PDF)
dc.identifier.urihttps://hdl.handle.net/2077/72131
dc.description.abstractArsenic is prevalent in the environment and this toxic metalloid poses a substantial threat to human health with 100-200 million people worldwide estimated to be at risk. Chronic exposure to arsenic is associated with neurodegenerative and age-related disorders that are characterized by the accumulation of protein aggregates, including Parkinson’s and Alzheimer’s disease. Despite of the undisputed toxicity of arsenic, our understanding of the underlying mechanisms and cellular responses is limited. This thesis has focused on arsenic-induced protein aggregation and toxicity in yeast, with the aim of elucidating how these aggregates are formed in vivo, the mechanisms by which they affect cells, how cells prevent their accumulation as well as how cells regulate the protein quality-control system to protect against toxic aggregates. The impact arsenic has on protein homeostasis may contribute to its toxicity and suspected role in protein misfolding diseases. Main findings of this thesis include the identification of novel genes whose overexpression conferred arsenic resistance. We also demonstrated the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. In addition, we showed that the ubiquitin-proteasome system (UPS) is the main pathway that clears arsenite-induced aggregates, whilst the autophagy-vacuole pathway and the chaperone-mediated disaggregation both contribute to clearance but their roles appear less prominent than the UPS. Our findings provide novel insights into the biology of arsenic and a valuable resource for further studies on the mechanistic details of arsenic toxicity and pathogenesis.en
dc.language.isoengen
dc.relation.haspartPaper 1 Identification of novel arsenic resistance genes in yeast. Isik et al., 2022. MicrobiologyOpen, https://doi.org/10.1002/mbo3.1284en
dc.relation.haspartPaper 2 Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity. Andersson et al., 2021. Journal of Cell Science, https://doi.org/10.1242/jcs.258338en
dc.relation.haspartPaper 3 Mechanisms mediating the clearance of arsenite-induced protein aggregates in Saccharomyces cerevisiae. Hua et al. (Unpublished manuscript 2022).en
dc.subjectArsenicen
dc.subjectProtein aggregationen
dc.subjectProtein quality controlen
dc.subjectYeasten
dc.titleArsenic-induced protein aggregation and toxicity in Saccharomyces cerevisiaeen
dc.typeTextswe
dc.type.svepDoctoral thesiseng
dc.gup.mailsansan.hua@gu.seen
dc.type.degreeDoctor of Philosophyen
dc.gup.originUniversity of Gothenburg, Faculty of Scienceen
dc.gup.departmentDepartment of Chemistry and Molecular Biology ; Institutionen för kemi och molekylärbiologien
dc.gup.defenceplaceFredagen den 30 september 2022, kl 9.00, Hörsal Karl Isaksson, Medicinaregatan 16en
dc.gup.defencedate2022-09-30
dc.gup.dissdb-fakultetMNF


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