Sister chromatid cohesion protein PDS5 homolog A (PDS5A)

Sister chromatid cohesion protein PDS5 homolog A (PDS5A) is a large, highly conserved cohesin-associated scaffold protein that plays a central role in organizing chromatin architecture and ensuring proper chromosome segregation during both mitosis and meiosis[4]. In vertebrates, PDS5A and its paralog PDS5B are critical regulators of the cohesin complex, which mediates sister chromatid cohesion, DNA repair, gene transcription, and DNA replication[1][4]. PDS5A interacts directly with cohesin subunits, including RAD21, and recruits regulatory factors such as the acetyltransferase ESCO1 and the cohesin-release factor WAPL, modulating the stability, localization, and dynamics of cohesin on chromatin[4]. It is essential for establishing and maintaining chromatin loop boundaries, particularly at CTCF sites, and controls the length and stability of these loops—key factors in three-dimensional genome organization and gene regulation[2][3]. PDS5A also stabilizes cohesin’s association with chromatin by promoting SMC3 acetylation, which is necessary for accurate sister chromatid cohesion[2]. Beyond its canonical role in cohesion, PDS5A modulates DNA replication dynamics by regulating the residence time of cohesin at replication forks, facilitating their progression and recruiting replication fork protection factors[2]. In oocytes, PDS5A has a non-canonical role in meiotic spindle assembly, where it localizes to spindle microtubules and is required for proper spindle elongation and chromosome segregation, independent of its cohesin-related functions[5]. Structurally, PDS5A consists of over 1,300 amino acids, with two large HEAT repeat clusters separated by a helical insert domain; these repeats serve as scaffolds for multiple protein-protein interactions[1][5]. The N-terminus is highly conserved between PDS5A and PDS5B, while the C-terminus harbors paralog-specific features, including differential phosphorylation sites that may underlie their distinct and overlapping roles in cellular processes[4]. Mutations or dysregulation of PDS5A have been implicated in cancer and cohesinopathies, underscoring its importance in maintaining genome integrity and normal development[4]. Despite its critical functions, there are currently no known drugs that specifically target PDS5A, and its potential as a therapeutic target remains under investigation.

Other names

Precocious dissociation of sisters 5 homolog AKIAA0648PIG54SCC-112SCC112cell proliferation-inducing gene 54 proteinSister chromatid cohesion protein 112regulator of cohesion maintenance homolog APDS5