Looping in on Ndc80 - how does a protein loop at the kinetochore control chromosome segregation?

TY - JOUR

T1 - Looping in on Ndc80 - how does a protein loop at the kinetochore control chromosome segregation?

AU - Nilsson, Jakob

N1 - Copyright © 2012 WILEY Periodicals, Inc.

PY - 2012/12

Y1 - 2012/12

N2 - Segregation of chromosomes during mitosis requires the interaction of dynamic microtubules with the kinetochore, a large protein structure established on the centromere region of sister chromatids. The core microtubule-binding activity of the kinetochore resides in the KMN network, an outer kinetochore complex. As part of the KMN network, the Ndc80 complex, which is composed of Ndc80, Nuf2, Spc24, and Spc25, is able to bind directly to microtubules and has the ability to track with depolymerizing microtubules to produce chromosome movement. The Ndc80 complex binds directly to microtubules through a calponin homology domain and an unstructured tail in the N terminus of the Ndc80 protein. A recent flurry of papers has highlighted the importance of an internal loop region in Ndc80 in establishing end-on attachment to microtubules. Here I discuss these recent findings that suggest that the Ndc80 internal loop functions as a binding site for proteins required for kinetochore-microtubule interactions. The proper segregation of chromosomes requires a stable yet dynamic binding between kinetochores and microtubules of the mitotic spindle. The kinetochore localized four-subunit Ndc80 complex plays a crucial role in establishing this link. Here I discuss our recent advance in understanding Ndc80 function and in particular an internal loop region.

AB - Segregation of chromosomes during mitosis requires the interaction of dynamic microtubules with the kinetochore, a large protein structure established on the centromere region of sister chromatids. The core microtubule-binding activity of the kinetochore resides in the KMN network, an outer kinetochore complex. As part of the KMN network, the Ndc80 complex, which is composed of Ndc80, Nuf2, Spc24, and Spc25, is able to bind directly to microtubules and has the ability to track with depolymerizing microtubules to produce chromosome movement. The Ndc80 complex binds directly to microtubules through a calponin homology domain and an unstructured tail in the N terminus of the Ndc80 protein. A recent flurry of papers has highlighted the importance of an internal loop region in Ndc80 in establishing end-on attachment to microtubules. Here I discuss these recent findings that suggest that the Ndc80 internal loop functions as a binding site for proteins required for kinetochore-microtubule interactions. The proper segregation of chromosomes requires a stable yet dynamic binding between kinetochores and microtubules of the mitotic spindle. The kinetochore localized four-subunit Ndc80 complex plays a crucial role in establishing this link. Here I discuss our recent advance in understanding Ndc80 function and in particular an internal loop region.

KW - Amino Acid Sequence

KW - Animals

KW - Binding Sites

KW - Cell Cycle Proteins

KW - Chromosome Segregation

KW - DNA-Binding Proteins

KW - Humans

KW - Kinetochores

KW - Microtubule-Associated Proteins

KW - Microtubules

KW - Molecular Sequence Data

KW - Nuclear Proteins

KW - Protein Conformation

KW - Saccharomyces cerevisiae Proteins

KW - Schizosaccharomyces pombe Proteins

KW - Vertebrates

UR - http://www.scopus.com/record/display.url?eid=2-s2.0-84869126336&origin=inward&txGid=F07F751433000BFBF92F5A7058593DFC.53bsOu7mi7A1NSY7fPJf1g%3a1

U2 - 10.1002/bies.201200096

DO - 10.1002/bies.201200096

M3 - Review

C2 - 23154893

SN - 0265-9247

VL - 34

SP - 1070

EP - 1077

JO - BioEssays

JF - BioEssays

IS - 12

ER -