Faithful anaphase is ensured by Mis4, a sister chromatid cohesion molecule required in S phase and not destroyed in G1 phase.
The loss of sister chromatid cohesion triggers anaphase spindle movement. The budding yeast Mcd1/Scc1 protein, called cohesin, is required for associating chromatids, and proteins homologous to it exist in a variety of eukaryotes. Mcd1/Scc1 is removed from chromosomes in anaphase and degrades in G1. We show that the fission yeast protein, Mis4, which is required for equal sister chromatid separation in anaphase is a different chromatid cohesion molecule that behaves independent of cohesin and is conserved from yeast to human. Its inactivation in G1 results in cell lethality in S phase and subsequent premature sister chromatid separation. Inactivation in G2 leads to cell death in subsequent metaphase-anaphase progression but missegregation occurs only in the next round of mitosis. Mis4 is not essential for condensation, nor does it degrade in G1. Rather, it associates with chromosomes in a punctate fashion throughout the cell cycle. mis4 mutants are hypersensitive to hydroxyurea (HU) and UV irradiation but retain the ability to restrain cell cycle progression when damaged or sustaining a block to replication. The mis4 mutation results in synthetic lethality with a DNA ligase mutant. Mis4 may form a stable link between chromatids in S phase that is split rather than removed in anaphase.
Furuya
K
K
CREST Research Project, Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-oiwake-cho, Sakyo-ku, Kyoto 606, Japan.
Takahashi
K
K
Yanagida
M
M
D000705:Anaphase / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002842:Chromatids / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone; D017124:Conserved Sequence; D011088:DNA Ligases / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology*; D020043:Genes, Essential; D006801:Humans; D008677:Metaphase / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016196:S Phase / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; C490529:MCD1 protein, S cerevisiae; C115842:MIS4 protein, S pombe; D009687:Nuclear Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D011088:DNA Ligases