Abstract
Functional links connecting gene transcription and condensin-mediated chromosome condensation have been established in species ranging from prokaryotes to vertebrates. However, the exact nature of these links remains misunderstood. Here we show in fission yeast that the 3′ end RNA processing factor Swd2.2, a component of the Cleavage and Polyadenylation Factor (CPF), is a negative regulator of condensin-mediated chromosome condensation. Lack of Swd2.2 does not affect the assembly of the CPF but reduces its association with chromatin. This causes only limited, context-dependent effects on gene expression and transcription termination. However, CPF-associated Swd2.2 is required for the association of Protein Phosphatase 1 PP1Dis2 with chromatin, through an interaction with Ppn1, a protein that we identify as the fission yeast homologue of vertebrate PNUTS. We demonstrate that Swd2.2, Ppn1 and PP1Dis2 form an independent module within the CPF, which provides an essential function in the absence of the CPF-associated Ssu72 phosphatase. We show that Ppn1 and Ssu72, like Swd2.2, are also negative regulators of condensin-mediated chromosome condensation. We conclude that Swd2.2 opposes condensin-mediated chromosome condensation by facilitating the function of the two CPF-associated phosphatases PP1 and Ssu72.
Highlights
Mitotic chromosome condensation is essential for genome integrity
Failure to properly condense chromosomes prior to their segregation in mitosis can lead to genome instability
Previous observations showed that the localization of condensin is intimately linked to regions of high transcription, somewhat paradoxically, its association with chromatin is disrupted by a processive polymerase activity
Summary
Mitotic chromosome condensation is essential for genome integrity. These can lead to chromosome breaks and the irreparable loss of genetic information. A key driver of chromosome condensation is the highly conserved condensin complex (reviewed in [1]). With cohesin and the SMC5/6 complex, one of three highly conserved multi-subunit protein complexes containing two different proteins of the SMC (Structural Maintenance of Chromosome) family. Condensin is made of five sub-units (SMC2Cut, SMC4Cut, CAP-D2Cnd, CAP-GCnd and CAP-HCnd, name of the human protein followed by its name in fission yeast), which together form a protein ring big enough to entrap two chromatids. Condensin exhibits a DNA-dependent ATPase activity and a DNA supercoiling activity but how these enzymatic activities contribute to mitotic condensation remains elusive. A number of experimental evidence indicate that cis-acting elements facilitate the binding of condensin at specific loci, supporting the current view that the underlying mechanisms of condensin recruitment are, to some extent, locus-specific (reviewed in [1])
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