Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling

Author:

Hiruma Yoshitaka123,Sacristan Carlos23,Pachis Spyridon T.23,Adamopoulos Athanassios1,Kuijt Timo23,Ubbink Marcellus4,von Castelmur Eleonore1,Perrakis Anastassis1,Kops Geert J. P. L.23

Affiliation:

1. Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.

2. Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.

3. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.

4. Leiden Institute of Chemistry, Leiden University, Post Office Box 9502, 2300 RA Leiden, Netherlands.

Abstract

How cells sense connected chromosomes Cells have a “checkpoint” that pauses cell division until all chromosomes are properly arranged on the mitotic spindle to allow precise distribution of one copy of each chromosome to each daughter cell. Hiruma et al. and Ji et al. explain the molecular mechanism by which cells sense that they are ready to divide. The protein kinase MPS1 associates with a protein complex at the kinetochore of the chromosome. Its activity produces signals that pause the cell cycle. When the chromosome becomes properly attached to the mitotic spindle, microtubules of the spindle physically compete for binding to the same site on the kinetochore where MPS1 is bound. Thus, once the kinetochore is properly attached, MPS1 dissociates, the inhibitory signal is lost, and cell division is allowed to proceed. Science , this issue pp. 1264 and 1260

Funder

KWF

SNF

ERC

NWO

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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