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Reference - PMID:28438891 - A second Wpl1 anti-cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP4.

Reference summary

PubMed ID
PMID:28438891
Title
A second Wpl1 anti-cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP4.
Authors
Birot A, Eguienta K, Vazquez S, Claverol S, Bonneu M, Ekwall K, Javerzat JP, Vaur S
Citation
EMBO J 2017 May 15;36(10):1364-1378
Publication year
2017
Abstract
Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl-transferase (Eso1 in fission yeast) counteracting Wpl1, promoting cohesin release from DNA We report here that Wpl1 anti-cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co-immunoprecipitated Wpl1 and cohesin and Wpl1 triggered Rad21 de-phosphorylation in a PP4-dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho-mimicking alleles dampened Wpl1 anti-cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter cohesin from Wpl1 unless erased by PP4. Experiments in post-replicative cells lacking Eso1 revealed two cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4-independent manner. Type 2 cohesin, however, remained DNA-bound and lost its cohesiveness in a manner depending on Wpl1- and PP4-mediated Rad21 de-phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the cohesin kleisin subunit.

Annotation

GO biological process

GO:0045875 - negative regulation of sister chromatid cohesion

Genes:

GO cellular component

GO:0000785 - chromatin

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GO molecular function

GO:0005515 - protein binding

Genes:

GO:0072542 - protein phosphatase activator activity

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GO:0004722 - protein serine/threonine phosphatase activity

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Modification

MOD:00046 - O-phospho-L-serine

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Multi-locus phenotype

FYPO:0000046 - decreased cell population growth

Genes:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

FYPO:0001357 - normal vegetative cell population growth

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Genotypes:

FYPO:0002060 - viable vegetative cell population

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Genotypes:

Single locus phenotype

FYPO:0002678 - abolished protein phosphorylation

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Genotypes:

FYPO:0001038 - increased protein phosphorylation during vegetative growth

Genes:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

Genes:

Genotypes:

FYPO:0004422 - normal protein phosphorylation

Genes:

Genotypes: