rine residues 10 and 28 by Aurora kinases and at threonine residue 3 by Haspin kinase. Since these phosphorylations generally coincide with chromosome condensation, they have been suggested as the driving factor for mitotic chromosome formation. Consistent with this notion are the findings that mutation of H3S10 to a non-phosphorylatable alanine residue results in chromosome segregation TG-02 chemical information defects in fission yeast and mitotically dividing micronuclei of the ciliated protozoan Tetrahymena thermophila. Simultaneous mutations of H3S10 and H3S28 to alanine in budding yeast has, in contrast, no appreciable effect on chromosome segregation or the step-wise conversion of the ribosomal RNA gene cluster into a loop-shaped structure. Moreover, incubation of human cultured cells with the phosphatase inhibitor okadaic acid results in H3S10 phosphorylation in the vast majority of cells, yet chromosomes condense only in a very small fraction of cells. Finally, a Drosophila mutant of the Aurora B kinase-associated Borealin protein still shows a remarkable degree of chromosome condensation, even though H3S10 phosphorylation can no longer be detected in the mutant. These observations imply that H3 phosphorylation cannot be the universal determinant of mitotic chromosome condensation. This conclusion is furthermore supported by the findings that in maize, H3S10 and H3S28 phosphorylation can only be detected on pericentric chromosome regions and only late during mitotic prophase, i.e. after mitotic chromosomes have already started to form. It is, however, conceivable that, in plants, phosphorylation of H3T3 by Haspin kinase might compensate for a lack of H3S10 and H3S28 phosphorylation on chromosome arms. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19809023 A recent report nevertheless proposed a specific role of H3 phosphorylation during chromosome condensation in yeast. Activation of photo-reactive residues introduced into histone H2A generated cross-links with the N-terminal tail of histone H4. The small fraction of cross-linked H4 observed in interphase cells increased $threefold as cells entered mitosis, suggesting that the interaction between H2A and H4 might be related to chromosome condensation. Moreover, mutation of H3S10 to alanine prevented cross-linking and mitosis-specific deacetylation of histone H4 lysine residue 16. Based on these observations, the authors proposed that deacetylation of H4K16, as a result of phospho-H3S10-mediated recruitment of the deacetylase Hst2, promotes the interaction of the histone H4 tail with an acetic patch on histone H2A of neighboring nucleosomes, resulting in chromosome condensation. However, the suggestion that this mechanism drives condensation in yeast is problematic for several reasons. As mentioned before, mutation of H3S10 to alanine does not notably affect cell division and rDNA condensation and results in only minimal defects in the condensation of a yeast fusion chromosome during anaphase; significantly less than the defects caused, for example, by inactivation of condensin . Likewise, deletion of the gene encoding the Hst2 deacetylase has 
no obvious effect on cell divisions and results in merely marginal condensation defects. Even when taking into account the difficulties in obtaining synchronous cell cycle populations by nocodazole washout, one would have expected to observe H4K16 deacetylation and H2AH4 cross-linking when chromosomes condense as cells proceeded from the arrest into anaphase, which was not the case. While it is likely that chromatin mod