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Protein Complexes in the Nucleus: The Control of Chromosome Segregation

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Macromolecular Protein Complexes

Part of the book series: Subcellular Biochemistry ((SCBI,volume 83))

Abstract

Mistakes in the process of cell division can lead to the loss, gain or rearrangement of chromosomes. Significant chromosomal abnormalities are usually lethal to the cells and cause spontaneous miscarriages. However, in some cases, defects in the spindle assembly checkpoint lead to severe diseases, such as cancer and birth and development defects, including Down’s syndrome. The timely and accurate control of chromosome segregation in mitosis relies on the spindle assembly checkpoint (SAC), an evolutionary conserved, self-regulated signalling system present in higher organisms. The spindle assembly checkpoint is orchestrated by dynamic interactions between spindle microtubules and the kinetochore , a multiprotein complex that constitutes the site for attachment of chromosomes to microtubule polymers to pull sister chromatids apart during cell division. This chapter discusses the current molecular understanding of the essential, highly dynamic molecular interactions underpinning spindle assembly checkpoint signalling and how the complex choreography of interactions can be coordinated in time and space to finely regulate the process. The potential of targeting this signalling pathway to interfere with the abnormal segregation of chromosomes, which occurs in diverse malignancies and the new opportunities that recent technological developments are opening up for a deeper understanding of the spindle assembly checkpoint are also discussed.

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Abbreviations

APC/C:

Anaphase Promoting Complex/Cyclosome

ATP:

Adenosine triphosphate

Bub1:

Budding uninhibited by benzimidazoles 1

BubR1:

Budding uninhibited by benzimidazoles related 1

CCAN:

Centromeric nucleosome-associated network

Cdc20:

Cell division cycle protein 20

CENP-E:

Centromere-associated protein E

CENP-F:

Centromere-associated protein F

CIN:

Chromosomal instability

CLASP-1:

CLIP-associating protein 1

CLASP-2:

CLIP-associating protein 2

FRET:

Förster resonance energy transfer

KMN:

KNL1/Mis12/Ndc80 network

KNL1:

Kinetochore-null phenotype 1

Mad1:

Mitotic arrest deficient 1

Mad2:

Mitotic arrest deficient 2

MIND complex:

Mis12 complex

Mps1:

Monopolar spindle 1

NMR:

Nuclear magnetic resonance

ROD:

Rough deal

RZZ-complex:

Rod, Zwilch and ZW10 complex

SAC:

Spindle assembly checkpoint

SAXS:

Small angle x-ray scattering

Spc105:

Spindle pole body 105

Spc105-related:

Spc105R

TEM:

cryo-transmission electron microscopy

XFEL:

Ultrafast X-ray free-electron laser

ZW10:

Zeste-white 10

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  1. Faculty of Health and Life Sciences, Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, OX3 0BP, UK

    Victor M. Bolanos-Garcia

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  1. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom

    Jon Marles-Wright

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Bolanos-Garcia, V.M. (2017). Protein Complexes in the Nucleus: The Control of Chromosome Segregation. In: Harris, J., Marles-Wright, J. (eds) Macromolecular Protein Complexes. Subcellular Biochemistry, vol 83. Springer, Cham. https://doi.org/10.1007/978-3-319-46503-6_16

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