PP2A Cdc55 dephosphorylates Pds1 and inhibits spindle elongation in S. cerevisiae

• Published in: Journal of cell science Vol. 133; no. 14
• Main Authors: Khondker, Shoily, Kajjo, Sam, Chandler-Brown, Devon, Skotheim, Jan, Rudner, Adam, Ikui, Amy E.
• Format: Journal Article
• Language: English
• Published: England 29-07-2020
• Subjects: Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosome Segregation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphorylation; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - metabolism; Protein Serine-Threonine Kinases - genetics; Protein-Tyrosine Kinases; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Securin; Separase; Spindle Apparatus - metabolism; Spindle; Pds1; PP2A; Cdc55; Esp1; S. cerevisiae
• ISSN: 1477-9137

PP2A
(the form of protein phosphatase 2A containing Cdc55) regulates cell cycle progression by reversing cyclin-dependent kinase (CDK)- and polo-like kinase (Cdc5)-dependent phosphorylation events. In
, Cdk1 phosphorylates securin (Pds1), which facilitates Pds1 binding and inhibits separase (Esp1). During anaphase, Esp1 cleaves the cohesin subunit Scc1 and promotes spindle elongation. Here, we show that PP2A
directly dephosphorylates Pds1 both
and
Pds1 hyperphosphorylation in a
deletion mutant enhanced the Pds1-Esp1 interaction, which played a positive role in Pds1 nuclear accumulation and in spindle elongation. We also show that nuclear PP2A
plays a role during replication stress to inhibit spindle elongation. This pathway acted independently of the known Mec1, Swe1 or spindle assembly checkpoint (SAC) checkpoint pathways. We propose a model where Pds1 dephosphorylation by PP2A
disrupts the Pds1-Esp1 protein interaction and inhibits Pds1 nuclear accumulation, which prevents spindle elongation, a process that is elevated during replication stress.