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VOL. 73 (4), 901-925, 2007 ROLES OF PROTEIN PHOSPHATASE TYPE 1...

reported a correlation between the phosphorylation of histone H3
along chromosomes in G2 and chromosome condensation (35, 37,
38) and also between chromosome decondensation in telophase and
PP1 activity or histone H3 dephosphorylation (39, 40). Accordingly,
in fission yeast and in Drosophila, phosphorylation of histone H3 by
Ark1 and Aurora B, respectively, is involved in the recruitment of
condensin complex to mitotic chromatin, and chromosome
condensation (36, 37, 41). Moreover, it has been published that
histone H3 is an in vivo mitotic substrate of PP1 in budding yeast
(35) and an in vitro one in Xenopus (42). These observations have led
to the hypothesis that chromosome (de)condensation requires
histone H3 (de)phosphorylation. However, differences seem to
exist between species since mutation of Ser 10 of histone H3 to
alanine did not cause any observable growth defect in budding yeast
(35) and neither Ser 10 nor the entire N-terminal tail of Xenopus
histone H3 is essential for chromosome condensation (43). The
histone H3 kinase activity of Xenopus Aurora-B depends on its
phosphorylation by an unknown kinase, which may well be Aurora-
B itself, as its budding yeast counterpart, Ipl1, is known to undergo
autophosphorylation (42-44). Interestingly, in Xenopus this Aurora-
B activation has been shown to be antagonized by PP1 (42).

Although the antagonistic relationship between Aurora and PP1
seems to be conserved from yeast to human, the possible interaction
in fission yeast between Ark1 and Dis2/Sds21 and the involvement of
Dis2/Sds21 in the dephosphorylation of H3 have not been studied
yet. Interestingly, ark1+ overexpression greatly inhibited cell growth
of the cold sensitive conditional dis2.11 mutant at the permissive
temperature, and exacerbated the mitotic defects of dis2.11 resulting
in a complete absence of colony formation at the restrictive
temperature (our unpublished results). Wild type cells tolerate ark1+
overexpression, and only display a minor phenotype, as 3% of the
population prematurely commit to mitosis (36). Thus, the effect of
ark1+ overexpression in dis2.11 could suggest a genetic interaction
between dis2+ and ark1+ and antagonising relationship between these
proteins in S. pombe.

Recently it has been suggested that Dis2 controls the release of
cells from the G2 DNA damage checkpoint (45, 46). Dis2
overexpression sensitises cells to DNA damage so that they are unable

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