PDS5A (PDS5 Cohesin Associated Factor A) is a regulatory subunit of the cohesin complex that modulates cohesin dynamics, stability, and chromatin association. Together with its paralog PDS5B, PDS5A forms a flexible interface that interacts with cohesin core subunits and regulatory factors like WAPL and SORORIN to control sister chromatid cohesion, DNA repair, and gene expression[@losada2005].
Function
Cohesin Regulation
PDS5A binds to the cohesin complex and:
Stabilizes cohesin-chromatin interactions: Protects cohesin from premature release
Recruits WAPL: Mediates the prophase pathway of cohesin removal
Interacts with SORORIN: Balances cohesive vs. non-cohesive cohesin states[@shintomi2009]
PDS5A (PDS5 Cohesin Associated Factor A) is a regulatory subunit of the cohesin complex that modulates cohesin dynamics, stability, and chromatin association. Together with its paralog PDS5B, PDS5A forms a flexible interface that interacts with cohesin core subunits and regulatory factors like WAPL and SORORIN to control sister chromatid cohesion, DNA repair, and gene expression[@losada2005].
Function
Cohesin Regulation
PDS5A binds to the cohesin complex and:
Stabilizes cohesin-chromatin interactions: Protects cohesin from premature release
Recruits WAPL: Mediates the prophase pathway of cohesin removal
Interacts with SORORIN: Balances cohesive vs. non-cohesive cohesin states[@shintomi2009]
Sister Chromatid Cohesion
PDS5A is essential for:
Cohesion establishment: Working with ESCO1/ESCO2 acetyltransferases
Cohesion maintenance: Protecting established cohesion during G2
Controlled release: Enabling proper chromosome segregation at anaphase[@dorsett2012]
Gene Regulation
In non-dividing cells, PDS5A influences:
CTCF binding: Modulating cohesin-CTCF interactions at TAD boundaries
[Human Protein Atlas: PDS5A](https://www.proteinatlas.org/ENSG00000121570-PDS5A)
References
[Losada A, et al, Identification of the vertebrate cohesin regulatory subunit PDS5 (2005)](https://doi.org/10.1016/j.cell.2005.10.047)
[Shintomi K, Hirano T, Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl-Pds5 and Sgo1 (2009)](https://doi.org/10.1101/gad.1844409)
[Dorsett D, Strom L, The ancient and evolving roles of cohesin in gene expression and DNA repair (2012)](https://doi.org/10.1016/j.cub.2012.02.046)
[Merkenschlager M, Odom DT, CTCF and cohesin: linking gene regulatory elements with disease genes (2013)](https://doi.org/10.1016/j.cell.2013.02.029)
[Watrin E, Peters JM, The cohesin complex is required for the DNA damage-induced G2/M checkpoint (2006)](https://doi.org/10.1016/j.molcel.2006.07.018)
[Gil-Rodriguez MC, et al, De novo heterozygous mutations in PDS5A in patients with Cornelia de Lange syndrome (2015)](https://doi.org/10.1038/ejhg.2015.45)
[Kon A, et al, Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms (2013)](https://doi.org/10.1038/ng.2731)
[Zhang B, et al, Dosage effects of cohesin regulatory factor PDS5 on chromatin cohesion and gene expression (2019)](https://doi.org/10.1371/journal.pgen.1008217)
[Mondal G, et al, Functional consequences of mutations in the cohesin acetyltransferase ESCO1 in cancer (2020)](https://doi.org/10.1016/j.celrep.2020.107939)