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primary topic: {SNG2}, a prion form of {Cut4/Apc1}, confers non-Mendelian inheritance of heterochromatin silencing defect in fission yeast

{SNG2}, a prion form of {Cut4/Apc1}, confers non-Mendelian inheritance of heterochromatin silencing defect in fission yeast
type: AcademicArticle
type: Article
abstract: Prions represent epigenetic regulator proteins that can self-propagate their structure and confer their misfolded structure and function on normally folded proteins. Like the mammalian prion PrPSc, prions also occur in fungi. While a few prions, like Swi1, affect gene expression, none are shown to affect heterochromatin structure and function. In fission yeast and metazoans, histone methyltransferase Clr4/Suv39 causes H3-Lys9 methylation, which is bound by the chromodomain protein Swi6/HP1 to assemble heterochromatin. Earlier, we showed that sng2-1 mutation in the Cut4 subunit of anaphase-promoting complex abrogates heterochromatin structure due to defective binding and recruitment of Swi6. Here, we demonstrate that the Cut4p forms a non-canonical prion form, designated as SNG2, which abrogates heterochromatin silencing. SNG2 exhibits various prion-like properties, e.g. non-Mendelian inheritance, requirement of Hsp proteins for its propagation, de novo generation upon cut4 overexpression, reversible curing by guanidine, cytoplasmic inheritance and formation of infectious protein aggregates, which are dissolved upon overexpression of hsp genes. Interestingly, SNG2 prion imparts an enhanced tolerance to stress conditions, supporting its role in promoting cell survival under environmental stress during evolution.
date: 2024-12
volume: 52
issue: 22
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

Oxford University Press (OUP)
type: Organization

Nucleic Acids Res.
type: Collection

Jagmohan Singh
type: Person
given name: Jagmohan
family name: Singh

Suchita Srivastava
type: Person
given name: Suchita
family name: Srivastava

Suman Sharma
type: Person
given name: Suman
family name: Sharma

Poonam Mishra
type: Person
given name: Poonam
family name: Mishra

Rudra Narayan Dubey
type: Person
given name: Rudra Narayan
family name: Dubey

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primary topic: {SNG2}, a prion form of {Cut4/Apc1}, confers non-Mendelian inheritance of heterochromatin silencing defect in fission yeast