Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis

Yuya Kagami; Keishi Nihira; Shota Wada; Masaya Ono; Mariko Honda; Kiyotsugu Yoshida

doi:10.1083/jcb.201308172

Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis

J Cell Biol. 2014 Jun 23;205(6):781-90. doi: 10.1083/jcb.201308172. Epub 2014 Jun 16.

Authors

Yuya Kagami¹, Keishi Nihira², Shota Wada¹, Masaya Ono³, Mariko Honda⁴, Kiyotsugu Yoshida⁵

Affiliations

¹ Department of Biochemistry and Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
² Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
³ Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
⁴ Department of Biochemistry and Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, JapanDepartment of Biochemistry and Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
⁵ Department of Biochemistry and Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan kyoshida@jikei.ac.jp.

Abstract

During mitosis, genomic DNA is condensed into chromosomes to promote its equal segregation into daughter cells. Chromosome condensation occurs during cell cycle progression from G2 phase to mitosis. Failure of chromosome compaction at prophase leads to subsequent misregulation of chromosomes. However, the molecular mechanism that controls the early phase of mitotic chromosome condensation is largely unknown. Here, we show that Mps1 regulates initial chromosome condensation during mitosis. We identify condensin II as a novel Mps1-associated protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492 during mitosis, and this phosphorylation event is required for the proper loading of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of condensin II and accurate chromosome condensation during prophase. These findings demonstrate that Mps1 governs chromosomal organization during the early stage of mitosis to facilitate proper chromosome segregation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / analysis
Adenosine Triphosphatases / metabolism*
Cell Cycle Proteins / analysis
Cell Cycle Proteins / metabolism
Cell Cycle Proteins / physiology*
Cell Nucleus / metabolism
Chromosomal Proteins, Non-Histone / chemistry
Chromosomal Proteins, Non-Histone / metabolism
Chromosomes / metabolism*
DNA-Binding Proteins / analysis
DNA-Binding Proteins / metabolism*
G2 Phase Cell Cycle Checkpoints
HEK293 Cells
HeLa Cells
Humans
Mitosis / physiology
Multiprotein Complexes / analysis
Multiprotein Complexes / metabolism*
Phosphorylation
Protein Serine-Threonine Kinases / analysis
Protein Serine-Threonine Kinases / metabolism
Protein Serine-Threonine Kinases / physiology*
Protein-Tyrosine Kinases / analysis
Protein-Tyrosine Kinases / metabolism
Protein-Tyrosine Kinases / physiology*
Serine / metabolism

Substances

Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Multiprotein Complexes
condensin complexes
Serine
Protein-Tyrosine Kinases
Protein Serine-Threonine Kinases
TTK protein, human
Adenosine Triphosphatases