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Reference - PMID:11387218 - A role for DNA polymerase alpha in epigenetic control of transcriptional silencing in fission yeast.

Reference summary

PubMed ID
PMID:11387218
Title
A role for DNA polymerase alpha in epigenetic control of transcriptional silencing in fission yeast.
Authors
Nakayama Ji, Allshire RC, Klar AJ, Grewal SI
Citation
EMBO J 2001 Jun 01;20(11):2857-66
Publication year
2001
Abstract
In the fission yeast Schizosaccharomyces pombe, transcriptional silencing at the mating-type region, centromeres and telomeres is epigenetically controlled, and results from the assembly of higher order chromatin structures. Chromatin proteins associated with these silenced loci are believed to serve as molecular bookmarks that help promote inheritance of the silenced state during cell division. Specifically, a chromodomain protein Swi6 is believed to be an important determinant of the epigenetic imprint. Here, we show that a mutation in DNA polymerase alpha (pol(alpha)) affects Swi6 localization at the mating-type region and causes a 45-fold increase in spontaneous transition from the silenced epigenetic state to the expressed state. We also demonstrate that pol(alpha) mutant cells are defective in Swi6 localization at centromeres and telomeres. Genetic analysis suggests that Polalpha and Swi6 are part of the same silencing pathway. Interestingly, we found that Swi6 directly binds to Pol(alpha) in vitro. Moreover, silencing-defective mutant Pol(alpha) displays reduced binding to Swi6 protein. This work indicates involvement of a DNA replication protein, Pol(alpha), in heterochromatin assembly and inheritance of epigenetic chromatin structures.

Annotation

Multi-locus phenotype

FYPO:0002336 - normal chromatin silencing at silent mating-type cassette

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FYPO:0004378 - normal protein localization to heterochromatin at silent mating-type cassette

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Single locus phenotype

FYPO:0003217 - decreased chromatin silencing at centromere central core

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FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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FYPO:0002827 - decreased chromatin silencing at silent mating-type cassette

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FYPO:0003573 - decreased protein localization to heterochromatin at silent mating-type cassette

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FYPO:0002386 - decreased protein localization to pericentric heterochromatin at centromere outer repeat region

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FYPO:0002387 - decreased protein localization to subtelomeric heterochromatin during vegetative growth

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FYPO:0004376 - increased chromatin silencing at silent mating-type cassette

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FYPO:0004377 - increased protein localization to heterochromatin at silent mating-type cassette

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FYPO:0002541 - increased protein localization to nucleoplasm

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