Cell cycle - Chromosome condensation in prometaphase

Chromosome condensation in prometaphase

The two critical steps in cell reproduction are to duplicate the DNA content of chromosomes and to segregate them into two daughter cells. The linkage between duplicated chromosomes is established during S phase (cohesion), it persists during their dramatic structural changes in prometaphase (condensation), and is finally dissolved at the metaphase-anaphase transition (separation) [1].

Chromosome condensation is a highly ordered process in which the two sister chromatids are sorted out and compacted without losing linkage between them. Condensin complex is one of the most abundant components of mitotic chromosome condensation distributed throughout the chromosome arms. The complex consists of two structural maintenance of chromosomes (SMC) subunits and three non-SMC subunits. SMC subunits are chromosome-associated protein C (CAP-C) and chromosome-associated protein E. Non-SMC subunits are Chromosome-associated protein D2 or D3 (CAP-D2/D3), Chromosome-associated protein G or G2 (CAP-G/G2) and Chromosome-associated protein H or H2 (CAP-H/CAP-H2) [2].

Condensin complex is stimulated by A-kinase anchoring protein (AKAP8) [3] and Cyclin-dependent kinase 1 (CDK1) phosphorylation. Phosphorylated by Cdk1/Cyclin B, Condensin complex gains the ability to introduce positive supercoils into DNA in the presence of ATP and Topoisomerase I (TOP I) [4], [5].

In addition, Condensin complex also converts nicked circular DNA into a positively knotted form in the presence of ATP and Topoisomerase II (TOP II) [4].

Phosphorylated at Ser10, Histone H3 takes part in chromosome condensation. Serine/threonine kinase 6 (Aurora-A) and Serine/threonine kinase 12 (Aurora-B) bind the Histone H3 N-terminal tail, and both phosphorylate Ser 10. The two kinases have a mutually exclusive localization: while Aurora-A is present in the centrosomes, Aurora-B co-localizes with the phosphorylated form of Histone H3 [6]. Besides, CDK1 phosphorylates Histone H1 and Histon H3 [7].

Condensin complex is colocalized with phosphorylated Histone H3 during the early stage of themitotic chromosome condensation [8].

References:

1. Hirano T
   Chromosome cohesion, condensation, and separation. Annual review of biochemistry 2000;69:115-44
2. Losada A, Hirano T
   Shaping the metaphase chromosome: coordination of cohesion and condensation. BioEssays : news and reviews in molecular, cellular and developmental biology 2001 Oct;23(10):924-35
3. Eide T, Carlson C, Tasken KA, Hirano T, Tasken K, Collas P
   Distinct but overlapping domains of AKAP95 are implicated in chromosome condensation and condensin targeting. EMBO reports 2002 May;3(5):426-32
4. Kimura K, Cuvier O, Hirano T
   Chromosome condensation by a human condensin complex in Xenopus egg extracts. The Journal of biological chemistry 2001 Feb 23;276(8):5417-20
5. Kimura K, Hirano M, Kobayashi R, Hirano T
   Phosphorylation and activation of 13S condensin by Cdc2 in vitro. Science (New York, N.Y.) 1998 Oct 16;282(5388):487-90
6. Crosio C, Fimia GM, Loury R, Kimura M, Okano Y, Zhou H, Sen S, Allis CD, Sassone-Corsi P
   Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Molecular and cellular biology 2002 Feb;22(3):874-85
7. Casta?o IB, Brzoska PM, Sadoff BU, Chen H, Christman MF
   Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae. Genes & development 1996 Oct 15;10(20):2564-76
8. Schmiesing JA, Gregson HC, Zhou S, Yokomori K
   A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation. Molecular and cellular biology 2000 Sep;20(18):6996-7006