Condensation of Prometaphase Chromosomes

Stable Identifier
Homo sapiens
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The condensin I complex is evolutionarily conserved and consists of five subunits: two SMC (structural maintenance of chromosomes) family subunits, SMC2 and SMC4, and three non-SMC subunits, NCAPD2, NCAPH and NCAPG. The stoichiometry of the complex is 1:1:1:1:1 (Hirano and Mitchinson 1994, Hirano et al. 1997, Kimura et al. 2001). SMC2 and SMC4 subunits, shared between condensin I and condensin II, are DNA-dependent ATPases, and condensins are able to introduce positive supercoils into DNA in an ATP-dependent manner (Kimura and Hirano 1997).

Protein levels of condensin subunits are constant during the cell cycle, however condensins are enriched on mitotic chromosomes. Four of the five subunits, SMC4, NCAPD2, NCAPG and NCAPH, are phosphorylated in both mitotic and interphase HeLa cells, but on different sites (Takemoto et al. 2004). CDK1 (CDC2) in complex with CCNB (cyclin B) phosphorylates NCAPD2, NCAPG and NCAPH in mitosis (Kimura et al. 1998, Kimura et al. 2001, Takemoto et al. 2006, Murphy et al. 2008), but other mitotic kinases, such as PLK1 (St-Pierre et al. 2009), and other post-translational modifications, such as acetylation, may also be involved (reviewed by Bazile et al. 2010). Global proteomic analysis of human cell lines has identified N6-acetylation of lysine residues in condensin subunits SMC2, SMC4 and NCAPH (Choudhary et al. 2009). Another high throughput proteomic study showed that condensin I subunits NCAPD2 and NCAPH are phosphorylated upon DNA damage, probably by ATM or ATR kinase (Matsuoka et al. 2007).

As condensin I is cytosolic, it gains access to chromosomes only after the nuclear envelope breakdown at the start of prometaphase (Ono et al. 2004). Condensin I, activated by CDK1-mediated phosphorylation, promotes hypercondensation of chromosomes that were condensed in prophase through the action of condensin II (Hirota et al. 2004). AURKB may also regulate association of condensin I complex with chromatin (Lipp et al. 2007). Protein phosphatase PP2A acts independently of its catalytic activity to target condensin II complex to chromatin, but does not interact with condensin I (Takemoto et al. 2009). Full activation of condensin I requires dephosphorylation of sites modified by CK2 during interphase (Takemoto et al. 2006). Besides being essential for chromosome condensation in mitosis, condensin I may also contribute to cohesin removal from chromosome arms in prometaphase, but the exact mechanism is not known (Hirota et al. 2004).
Literature References
PubMed ID Title Journal Year
11136719 Chromosome condensation by a human condensin complex in Xenopus egg extracts

Cuvier, O, Kimura, K, Hirano, T

J. Biol. Chem. 2001
18977199 Phosphorylation of CAP-G is required for its chromosomal DNA localization during mitosis

Sarge, KD, Murphy, LA

Biochem. Biophys. Res. Commun. 2008
19608861 Lysine acetylation targets protein complexes and co-regulates major cellular functions

Rehman, M, Nielsen, ML, Olsen, JV, Walther, TC, Choudhary, C, Kumar, C, Gnad, F, Mann, M

Science 2009
17356064 Aurora B controls the association of condensin I but not condensin II with mitotic chromosomes

Hirota, T, Peters, JM, Poser, I, Lipp, JJ

J. Cell. Sci. 2007
9774278 Phosphorylation and activation of 13S condensin by Cdc2 in vitro

Hirano, M, Hirano, T, Kobayashi, R, Kimura, K

Science 1998
15572404 Distinct functions of condensin I and II in mitotic chromosome assembly

Hirota, T, Peters, JM, Koch, B, Ellenberg, J, Gerlich, D

J. Cell. Sci. 2004
15146063 Spatial and temporal regulation of Condensins I and II in mitotic chromosome assembly in human cells

Fang, Y, Spector, DL, Ono, T, Hirano, T

Mol. Biol. Cell 2004
20703077 Three-step model for condensin activation during mitotic chromosome condensation

St-Pierre, J, D'Amours, D, Bazile, F

Cell Cycle 2010
17525332 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage

Gygi, SP, Lerenthal, Y, Hurov, KE, Bakalarski, CE, Shiloh, Y, Smogorzewska, A, Ballif, BA, Zhao, Z, Elledge, SJ, Matsuoka, S, Luo, J, McDonald, ER, Solimini, N

Science 2007
9160743 Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein

Hirano, M, Hirano, T, Kobayashi, R

Cell 1997
9288743 ATP-dependent positive supercoiling of DNA by 13S condensin: a biochemical implication for chromosome condensation

Hirano, T, Kimura, K

Cell 1997
17066080 Negative regulation of condensin I by CK2-mediated phosphorylation

Kimura, K, Yanagisawa, J, Hanaoka, F, Takemoto, A, Yokoyama, S

EMBO J. 2006
19481522 Polo kinase regulates mitotic chromosome condensation by hyperactivation of condensin DNA supercoiling activity

St-Pierre, J, Ratsima, H, Pascariu, M, D'Amours, D, Bonneil, E, Bazile, F, Douziech, M, Sauvé, V

Mol. Cell 2009
19915589 The chromosomal association of condensin II is regulated by a noncatalytic function of PP2A

Imamoto, N, Kimura, K, Yanagisawa, J, Watanabe, Y, Murayama, A, Maeshima, K, Hirano, T, Imamura, S, Ikehara, T, Hanaoka, F, Takemoto, A, Yokoyama, S, Yamaguchi, K

Nat. Struct. Mol. Biol. 2009
14607834 Cell cycle-dependent phosphorylation, nuclear localization, and activation of human condensin

Kimura, K, Hanaoka, F, Takemoto, A, Yokoyama, S

J. Biol. Chem. 2004
7954811 A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro

Hirano, T, Mitchison, TJ

Cell 1994
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