Pds5 Regulates Sister-Chromatid Cohesion and Chromosome Bi-orientation through a Conserved Protein Interaction Module

• Published in: Current biology 2017-04, Vol.27 (7), p.1005-1012
• Main Authors: Goto, Yuhei, Yamagishi, Yuya, Shintomi-Kawamura, Miyuki, Abe, Mayumi, Tanno, Yuji, Watanabe, Yoshinori
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Aurora B; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosome Segregation; cohesin; CPC; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Eso1; Haspin; Humans; Pds5; Potassium Channels, Inwardly Rectifying - chemistry; Potassium Channels, Inwardly Rectifying - genetics; Potassium Channels, Inwardly Rectifying - metabolism; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - chemistry; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Sequence Alignment; Top2; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Wapl
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2017.02.066

Sister-chromatid cohesion is established by the cohesin complex in S phase and persists until metaphase, when sister chromatids are captured by microtubules emanating from opposite poles [1]. The Aurora-B-containing chromosome passenger complex (CPC) plays a crucial role in achieving chromosome bi-orientation by correcting erroneous microtubule attachment [2]. The centromeric localization of the CPC relies largely on histone H3-T3 phosphorylation (H3-pT3), which is mediated by the mitotic histone kinase Haspin/Hrk1 [3–5]. Hrk1 localization to centromeres depends largely on the cohesin subunit Pds5 in fission yeast [5]; however, it is unknown how Pds5 regulates Hrk1 localization. Here we identify a conserved Hrk1-interacting motif (HIM) in Pds5 and a Pds5-interacting motif (PIM) in Hrk1 in fission yeast. Mutations in either motif result in the displacement of Hrk1 from centromeres. We also show that the mechanism of Pds5-dependent Hrk1 recruitment is conserved in human cells. Notably, the PIM in Haspin/Hrk1 is reminiscent of the YSR motif found in the mammalian cohesin destabilizer Wapl and stabilizer Sororin, both of which bind PDS5 [6–12]. Similarly, and through the same motifs, fission yeast Pds5 binds to Wpl1/Wapl and acetyltransferase Eso1/Eco1, in addition to Hrk1. Thus, we have identified a protein-protein interaction module in Pds5 that serves as a chromatin platform for regulating sister-chromatid cohesion and chromosome bi-orientation. [Display omitted] •Haspin binds Pds5 through a conserved PIM-HIM interaction module•The Pds5-dependent Haspin localization mechanism is conserved from yeast to humans•Eso1 and Wpl1 also utilize the PIM-HIM interaction module for binding Pds5•Pds5 is a chromatin platform regulating both chromosome cohesion and bi-orientation The cohesin complex is responsible for multiple chromatin-related processes beyond sister-chromatid cohesion. Goto et al. report that the cohesin subunit Pds5 plays multiple roles in sister-chromatid cohesion and chromosome bi-orientation by interacting with Wpl1, Eso1, and Haspin through a conserved protein-protein interaction module.