The chromosomal association of condensin II is regulated by a noncatalytic function of PP2A

Abstract

Mitotic chromosomal assembly in vertebrates is regulated by condensin I and condensin II, which work cooperatively but have different chromosomal localization profiles and make distinct mechanistic contributions to this process. We show here that protein phosphatase 2A (PP2A), which interacts with condensin II but not condensin I, plays an essential role in targeting condensin II to chromosomes. Unexpectedly, our data indicate that PP2A acts as a recruiter protein rather than a catalytic enzyme to target condensin II to chromosomes. This recruiting activity of PP2A was inhibited by okadaic acid, but not by fostriecin, even though both molecules strongly inhibited the catalytic activity of PP2A. Additionally, we found that the chromokinesin KIF4a is also targeted to chromosomes via the noncatalytic activity of PP2A. Thus, our studies reveal a previously unknown contribution of PP2A to chromosome assembly.

Chromatin maintenance by a molecular motor protein

“…40 PP2A has also been shown to be involved in recruiting KIF4 onto mitotic chromosome arms. 9 Interestingly, PRC1, the protein regulator of cytokinesis and a KIF4 interacting protein, has been found to interact with HSF2 at the hsp70i promoter. 41 The binding of KIF4 to heat shock elements (HSE) in vitro ( Fig.…”

“…Interestingly, KIF4, PARP1 and condensin have all been shown to interact with each other 38 and interactions between condensin, KIF4 and PARP-1 10,18,38 may act in concert in chromosome structure maintenance and genome integrity. 9 Importantly, PARP-1 also interacts with condensins 38 and has recently been implicated in homologous recombination on damaged DNA. 9,39 Furthermore, the interaction between condensin and PARP-1 is particularly strong during S phase.…”

“…9 Importantly, PARP-1 also interacts with condensins 38 and has recently been implicated in homologous recombination on damaged DNA. 9,39 Furthermore, the interaction between condensin and PARP-1 is particularly strong during S phase. The heat shock protein HSF2 has been shown to recruit PP2A that inactivates condensin subunit CAP-G for transient "opening" of chromatin.…”

“…3,4 The chromokinesins are a subfamily of kinesins, which are characterized by their ability to bind to chromatin. 3,[5][6][7][8][9] Chromokinesins act in various steps of mitosis, including chromosome condensation, metaphase alignment, chromosome segregation, cytokinesis and they help maintain genome stability. 3,[10][11][12][13] The chromokinesin KIF4 associates with mitoic chromosomes and the central spindle and contributes to faithful chromosome segregation.…”

Optimization of calyculin A-induced premature chromosome condensation assay for chromosome aberration studies

“…However, the molecular details of how chromosome compaction is achieved during cell division are not clear. Recently, Takemoto et al (32) reported that PP2A interacts with condensin II but not condensin I and plays an essential role in targeting condensin II to chromosome. PP2A acts as a recruiter protein in the noncatalytic regulation, which is required for the chromosomal association of condensin II in human cells.…”