Pds5 Regulates Sister-Chromatid Cohesion and Chromosome Bi-orientation through a Conserved Protein Interaction Module.
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.
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan; Graduate Program in Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Yuhei
Y
Goto
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Yuya
Y
Yamagishi
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan; Graduate Program in Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Miyuki
M
Shintomi-Kawamura
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan; Graduate Program in Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Mayumi
M
Abe
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Yuji
Y
Tanno
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan; Graduate Program in Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan. Electronic address: ywatanab@iam.u-tokyo.ac.jp.
Yoshinori
Y
Watanabe
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C099489:KCNJ4 protein, human; C118660:PDS5B protein, human; D024661:Potassium Channels, Inwardly Rectifying; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C499666:pds5 protein, S pombe; C553145:Hrk1 protein, S pombe; D017346:Protein Serine-Threonine Kinases
Aurora B; CPC; Eso1; Haspin; Pds5; Top2; Wapl; cohesin