Hsk1- and SCFPof3-Dependent Proteolysis of S. pombe Ams2 Ensures Histone Homeostasis and Centromere Function

Schizosaccharomyces pombe GATA factor Ams2 is responsible for cell cycle-dependent transcriptional activation of all the core histone genes peaking at G1/S phase. Intriguingly, its own protein level also fluctuates concurrently. Here, we show that Ams2 is ubiquitylated and degraded through the SCF (Skp1-Cdc53/Cullin-1-F-box) ubiquitin ligase, in which F box protein Pof3 binds this protein. Ams2 is phosphorylated at multiple sites, which is required for SCFPof3-dependent proteolysis. Hsk1/Cdc7 kinase physically associates with and phosphorylates Ams2. Even mild overexpression of Ams2 induces constitutive histone expression and chromosome instability, and its toxicity is exaggerated when Hsk1 function is compromised. This is partly attributable to abnormal incorporation of canonical H3 into the central CENP-A/Cnp1-rich centromere, thereby reversing specific chromatin structures to apparently normal nucleosomes. We propose that Hsk1 plays a vital role during post S phase in genome stability via SCFPof3-mediated degradation of Ams2, thereby maintaining centromere integrity. [Display omitted] ► Cell cycle-regulated histone transcription factor Ams2 is stable only during G1/S ► Ams2 gets phosphorylated by DDK during S phase and presumably G2 phase ► Phosphorylated Ams2 is ubiquitylated by SCFpof3 and degraded via the proteasome ► Ectopic Ams2 expression interferes with histone homeostasis and centromere function