Mitotic chromosomes

Hirano T, Mitchison TJ 1994 A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro. Cell 79 449-458... 

Sigrist S, Jacobs H, Stratmann R, Lehner CF 1995 Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B and B3. EMBO J 14 4827-4838 Skibbens RV, Corson LB, Koshland D, Hieter P 1999 Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery. Genes... 

Vig BK 1981 Sequence of centromere separation analysis of mitotic chromosomes in man. Hum... 

Feng H, Zhong W, Punkosdy G et al 1999 CUL-2 is required for the Gl-to-S-phase transition and mitotic chromosome condensation in Caenorhabditis elegans. Nat Cell Biol 1 486-492 Hedgecock EM, White TG 1985 Polyploid tissue in the nematode Caenorhabditiselegans. Dev Biol 107 128-133... 

Parry JM, Danford N, Parry EM. 1984. In vitro techniques for the detection of chemicals capable of inducing mitotic chromosome aneuploidy. Altern Lab Anim 11 117-128. 

Crebelli, R., Andreoli, C., Carere, A., Conti, G., Conti, L., Cotta-Ramusino, M., Benigni, R. The induction of mitotic chromosome malsegregation in Aspergillus nidulans. Quantitative structure activity relationship (QSAR) analysis with chlorinated aliphatic hydrocarbons. Mutat. Res. 1992, 266, 117-134. 

The nucleosome is the building block of chromatin. Chromatin is a dynamic structure and it goes through several levels of compaction, reaching the very compact structure of mitotic chromosomes. 

Another group of non-histone proteins have been identified as essential components for the formation of the condensed chromosome (Table 1). Topoisomerase II (topo II) localizes in the scaffold/matrix fraction of the interphase nuclear (Berrios et al., 1985) and the mitotic chromosome (Maeshima and Laemmli, 2003) (see section 3.1). Topo II forms a ring-shaped homodimer (Berger et al, 1996 Nettikadan et al, 1998) and catalyzes the decatenation and relaxation of DNA double strand (Wang, 2002). In fission yeast, chromosomes cannot be condensed without functional topo II (Uemura et al, 1987). In addition, in in vitro experiment, mitotic extracts containing topo II induce chromatin condensation in the isolated nuclei from HeLa and chicken erythrocyte cells (Adachi et al., 1991). 

The condensin complex has been identified in the same scaffold fraction (Maeshima and Laemmli, 2003) and shown to be essential for the mitotic chromosome condensation (Hirano et al, 1997). The frog condensin complex exhibits ATP-dependent DNA-supercoiling activity (Kimura and Hirano, 1997). It consists of a heterodimer of SMC and a trimer of non-SMC proteins (Hirano et al, 1997). The SMC complex has a globular head domain and a coiled-coil tail region (Anderson et al., 2002 Melby et al, 1998 Yoshimura et al., 2002). In vertebrates, two types of condensin complex, condensin I and condensin II, exist they are composed of the same SMC subunits but with different non-SMC subunits (Ono et al, 2003). 

Phosphorylation has been thought to be correlated to the mitotic chromatin condensation and the transcriptional regulation in interphase (Nowak and Corces, 2004). The mitotic phosphorylation, which was first identified in 1978 (Gurley et al, 1978), occurs at Ser (Wei et al, 1998), Ser (Goto et al, 1999), and Thr (Preuss et al, 2003) in histone H3. The Ser phosphorylation is catalyzed by the aurora kinase family (de la Barre et al, 2000), and is required for the initiation of chromosome condensation but not for its maintenance (dephosphorylation of mitotic chromosomes does not induce chromosome decondensation) (Van Hooser et fl/.,1998). In meiosis, Ser phosphorylation is also required for the cohesion of sister chromatids rather than the condensation (Kaszas and Cande, 2000). 

It is interesting and important to note that several species, such as Schizosac-charomyces pombe, lack histone HI (Wood et al 2002) (see also section 2.4). The nucleosome-repeat length is slightly shorter in S. pombe than in human (Godde and Widom, 1992). The contribution of histone HI to the mitotic chromosome condensation has been examined with the use of a cell-free system of Xenopus eggs, in which the condensed sperm nuclei can be transformed into metaphase chromosomes. Even when histone HI is removed from the extract, the metaphase chromosomes can still be formed (Ohsumi et al, 1993). In addition, an elimination of all HI genes in Tetrahymena exerts no phenotypic effect (Shen et al, 1995). 

Lu W, Peterson R, Dasgupta A, Scovell WM (2000) Influence of HMG-1 and adenovirus oncoprotein ElA on early stages of transcriptional preinitiation complex assembly. J Biol Chem 275 35006-35012 Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucle-osome core particle at 2.8 A resolution. Nature 389 251—260 Lusser A, Kadonaga JT (2004) Strategies for the reconstitution of chromatin. Nat Methods 1 19-26 Maeshima K, Laemmli UK (2003) A two-step scaffolding model for mitotic chromosome assembly. Dev Cell 4 467-480... 

Olins DE, Olins AL (1972) Physical studies of isolated eucaryotic nuclei. J Cell Biol 53 715-736 Ono T, Losada A, Hirano M, Myers MP, Neuwald AF, Hirano T (2003) Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells. Cell 115 109-121... 

Uemura T, Ohkura H, Adachi Y, Morino K, Shiozaki K, Yanagida M (1987) DNA topoisomerase 11 is required for condensation and separation of mitotic chromosomes in S. pombe. Cell 50 917-925 Ushiki T, Hoshi O, Iwai K, Kimura E, Shigeno M (2002) The structure of human metaphase chromosomes its histological perspective and new horizons by atomic force microscopy. Arch Histol Cytol 65 377-390... 

Hendzel MJ, Wei Y, Mancini MA, Van Hooser A, Ranalh T, Brinkley BR, Bazett-Jones DP, Allis CD (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106(6) 348—360... 

During mitosis, aU the DNA is highly condensed to allow separation of the sister chromatids. This is the only time in the ceE cycle when the chromosome structure is visible. Chromosome abnormalities may be assessed on mitotic chromosomes by karyotype analysis (metaphase chromosomes) and by banding techniques (prophase or prometaphase), which identify aneu-ploidy, translocations, deletions, inversions, and duplications. 

Figure 1. Hierarchical structure of eukaryotic DNA. Each DNA molecule is packed into a mitotic chromosome that is 1/50,000 shorter than its extended length. (Adapted with permission from Macmillan Publishers Ltd. [25], copyright 2003).

S. cerevisiae aurora/IPllp, C. elegans aurora/AIR-2, and mammalian aurora B (also called AIM-1) phosphorylate H3 at Ser-10 and Ser-28 during mitosis [39 1] (Fig. 5). Protein phosphatase 1 removes the phosphate at these sites [39,42]. INCENP is bound to aurora B and is essential for the proper targeting of aurora B on the chromosomes [43-45]. INCENP and aurora B (AIM-1) are overexpressed in a variety of human cancers, including colorectal cancer [43,46]. Overexpression of aurora B (AIM-1) in CHE diploid fibroblasts leads to chromosomal instability, suggesting that aurora B overexpression may play a role in carcinogenesis [46]. INCENP/aurora B and H3 phosphorylation appear to be involved in assembly of mitotic chromosomes, but not mitotic chromosome compaction [44,47]. 

Ubiquitinated histones have been suggested to destabilize the interface between the H2A-H2B dimers and the H3-H4 tetramer [211], and to be depleted from highly condensed mitotic chromosomes and enriched in HI deficient chromatin [212]. In Drosophila, the inducible hsp70 and copia genes are ubiquitinated, which represents... 

Rice, J.D., Nishioka, K., Sarma, K., Steward, R., Reinberg, D., and Allis, C.D. (2002) Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes. Genes Dev. 16, 2225-2230. 

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