Targeting Plk1 to chromosome arms and regulating chromosome compaction by the PICH ATPase.
During mitosis, chromosomes undergo dynamic structural changes that include condensation of chromosomes-the formation of individual compact chromosomes necessary for faithful segregation of sister chromatids in anaphase. Polo-like kinase 1 (Plk1) regulates multiple mitotic events by binding to targeting factors at different mitotic structures in a phosphorylation dependent manner. In this study, we report the identification of a putative ATPase that targets Plk1 to chromosome arms during mitosis. PICH (Plk1-interacting checkpoint "helicase") displays a temporal localization on chromosome arms and kinetochores during early mitosis. Interaction with PICH recruits Plk1 to chromosome arms and disruption of this interaction abolishes Plk1 localization on chromosome arms. Moreover, depletion of PICH or overexpression of PICH mutant that is defective in Plk1 binding or ATP binding causes defects in mitotic chromosome compaction, formation of anaphase bridge and cytokinesis failure. We provide data to show that both PICH phosphorylation and its ATPase activity are required for mitotic chromosome compaction. Our study provides a mechanism for targeting Plk1 to chromosome arms and suggests that the PICH ATPase activity is important for the regulation of mitotic chromosome architecture.
Leng
Mei
M
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Besusso
Dario
D
Jung
Sung Yun
SY
Wang
Yi
Y
Qin
Jun
J
D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D004265:DNA Helicases; D017931:DNA Primers; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C516980:ERCC6L protein, human