The kinetochore proteins Pcs1 and Mde4 and heterochromatin are required to prevent merotelic orientation.
BACKGROUND
Accurate chromosome segregation depends on the establishment of correct-amphitelic-kinetochore orientation. Merotelic kinetochore orientation is an error that occurs when a single kinetochore attaches to microtubules emanating from opposite spindle poles, a condition that hinders segregation of the kinetochore to a spindle pole in anaphase. To avoid chromosome missegregation resulting from merotelic kinetochore orientation, cells have developed mechanisms to prevent or correct merotelic attachment. A protein called Pcs1 has been implicated in preventing merotelic attachment in mitosis and meiosis II in the fission yeast S. pombe.


RESULTS
We report that Pcs1 forms a complex with a protein called Mde4. Both Pcs1 and Mde4 localize to the central core of centromeres. Deletion of mde4(+), like that of pcs1(+), causes the appearance of lagging chromosomes during the anaphases of mitotic and meiosis II cells. We provide evidence that the kinetochores of lagging chromosomes in both pcs1 and mde4 mutant cells are merotelically attached. In addition, we find that lagging chromosomes in cells with defective centromeric heterochromatin also display features consistent with merotelic attachment.


CONCLUSIONS
We suggest that the Pcs1/Mde4 complex is the fission yeast counterpart of the budding yeast monopolin subcomplex Csm1/Lrs4, which promotes the segregation of sister kinetochores to the same pole during meiosis I. We propose that the Pcs1/Mde4 complex acts in the central kinetochore domain to clamp microtubule binding sites together, the centromeric heterochromatin coating the flanking domains provides rigidity, and both systems contribute to the prevention of merotelic attachment.
Gregan
Juraj
J
Max F. Perutz Laboratories, Department of Chromosome Biology, University of Vienna, Dr. Bohr-Gasse 1, 1030 Vienna, Austria. juraj.gregan@univie.ac.at
Riedel
Christian G
CG
Pidoux
Alison L
AL
Katou
Yuki
Y
Rumpf
Cornelia
C
Schleiffer
Alexander
A
Kearsey
Stephen E
SE
Shirahige
Katsuhiko
K
Allshire
Robin C
RC
Nasmyth
Kim
K
D018797:Cell Cycle Proteins / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology*; D006570:Heterochromatin / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D018386:Kinetochores / Q000378:metabolism / Q000502:physiology*; D013058:Mass Spectrometry; D008540:Meiosis / Q000502:physiology; D008780:Methyltransferases / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D046912:Multiprotein Complexes / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D006570:Heterochromatin; D046912:Multiprotein Complexes; D029702:Schizosaccharomyces pombe Proteins; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C112744:clr4 protein, S pombe