author_facet Desai, Arshad
Rybina, Sonja
Müller-Reichert, Thomas
Shevchenko, Andrej
Shevchenko, Anna
Hyman, Anthony
Oegema, Karen
Desai, Arshad
Rybina, Sonja
Müller-Reichert, Thomas
Shevchenko, Andrej
Shevchenko, Anna
Hyman, Anthony
Oegema, Karen
author Desai, Arshad
Rybina, Sonja
Müller-Reichert, Thomas
Shevchenko, Andrej
Shevchenko, Anna
Hyman, Anthony
Oegema, Karen
spellingShingle Desai, Arshad
Rybina, Sonja
Müller-Reichert, Thomas
Shevchenko, Andrej
Shevchenko, Anna
Hyman, Anthony
Oegema, Karen
Genes & Development
KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
Developmental Biology
Genetics
author_sort desai, arshad
spelling Desai, Arshad Rybina, Sonja Müller-Reichert, Thomas Shevchenko, Andrej Shevchenko, Anna Hyman, Anthony Oegema, Karen 0890-9369 1549-5477 Cold Spring Harbor Laboratory Developmental Biology Genetics http://dx.doi.org/10.1101/gad.1126303 <jats:p>Segregation of the replicated genome during cell division requires kinetochores, mechanochemical organelles that assemble on mitotic chromosomes to connect them to spindle microtubules. CENP-A, a histone H3 variant, and CENP-C, a conserved structural protein, form the DNA-proximal foundation for kinetochore assembly. Using RNA interference-based genomics in <jats:italic>Caenorhabditis elegans</jats:italic>, we identified KNL-1, a novel kinetochore protein whose depletion, like that of CeCENP-A or CeCENP-C, leads to a “kinetochore-null” phenotype. KNL-1 is downstream of CeCENP-A and CeCENP-C in a linear assembly hierarchy. In embryonic extracts, KNL-1 exhibits substoichiometric interactions with CeCENP-C and forms a near-stoichiometric complex with CeNDC-80 and HIM-10, the <jats:italic>C. elegans</jats:italic> homologs of Ndc80p/HEC1p and Nuf2p—two widely conserved outer kinetochore components. However, CeNDC-80 and HIM-10 are not functionally equivalent to KNL-1 because their inhibition, although preventing formation of a mechanically stable kinetochore-microtubule interface and causing chromosome missegregation, does not result in a kinetochore-null phenotype. The greater functional importance of KNL-1 may be due to its requirement for targeting multiple components of the outer kinetochore, including CeNDC-80 and HIM-10. Thus, KNL-1 plays a central role in translating the initiation of kinetochore assembly by CeCENP-A and CeCENP-C into the formation of a functional microtubule-binding interface.</jats:p> KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in <i>C. elegans</i> Genes & Development
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title KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_unstemmed KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_full KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_fullStr KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_full_unstemmed KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_short KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_sort knl-1 directs assembly of the microtubule-binding interface of the kinetochore in <i>c. elegans</i>
topic Developmental Biology
Genetics
url http://dx.doi.org/10.1101/gad.1126303
publishDate 2003
physical 2421-2435
description <jats:p>Segregation of the replicated genome during cell division requires kinetochores, mechanochemical organelles that assemble on mitotic chromosomes to connect them to spindle microtubules. CENP-A, a histone H3 variant, and CENP-C, a conserved structural protein, form the DNA-proximal foundation for kinetochore assembly. Using RNA interference-based genomics in <jats:italic>Caenorhabditis elegans</jats:italic>, we identified KNL-1, a novel kinetochore protein whose depletion, like that of CeCENP-A or CeCENP-C, leads to a “kinetochore-null” phenotype. KNL-1 is downstream of CeCENP-A and CeCENP-C in a linear assembly hierarchy. In embryonic extracts, KNL-1 exhibits substoichiometric interactions with CeCENP-C and forms a near-stoichiometric complex with CeNDC-80 and HIM-10, the <jats:italic>C. elegans</jats:italic> homologs of Ndc80p/HEC1p and Nuf2p—two widely conserved outer kinetochore components. However, CeNDC-80 and HIM-10 are not functionally equivalent to KNL-1 because their inhibition, although preventing formation of a mechanically stable kinetochore-microtubule interface and causing chromosome missegregation, does not result in a kinetochore-null phenotype. The greater functional importance of KNL-1 may be due to its requirement for targeting multiple components of the outer kinetochore, including CeNDC-80 and HIM-10. Thus, KNL-1 plays a central role in translating the initiation of kinetochore assembly by CeCENP-A and CeCENP-C into the formation of a functional microtubule-binding interface.</jats:p>
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author Desai, Arshad, Rybina, Sonja, Müller-Reichert, Thomas, Shevchenko, Andrej, Shevchenko, Anna, Hyman, Anthony, Oegema, Karen
author_facet Desai, Arshad, Rybina, Sonja, Müller-Reichert, Thomas, Shevchenko, Andrej, Shevchenko, Anna, Hyman, Anthony, Oegema, Karen, Desai, Arshad, Rybina, Sonja, Müller-Reichert, Thomas, Shevchenko, Andrej, Shevchenko, Anna, Hyman, Anthony, Oegema, Karen
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description <jats:p>Segregation of the replicated genome during cell division requires kinetochores, mechanochemical organelles that assemble on mitotic chromosomes to connect them to spindle microtubules. CENP-A, a histone H3 variant, and CENP-C, a conserved structural protein, form the DNA-proximal foundation for kinetochore assembly. Using RNA interference-based genomics in <jats:italic>Caenorhabditis elegans</jats:italic>, we identified KNL-1, a novel kinetochore protein whose depletion, like that of CeCENP-A or CeCENP-C, leads to a “kinetochore-null” phenotype. KNL-1 is downstream of CeCENP-A and CeCENP-C in a linear assembly hierarchy. In embryonic extracts, KNL-1 exhibits substoichiometric interactions with CeCENP-C and forms a near-stoichiometric complex with CeNDC-80 and HIM-10, the <jats:italic>C. elegans</jats:italic> homologs of Ndc80p/HEC1p and Nuf2p—two widely conserved outer kinetochore components. However, CeNDC-80 and HIM-10 are not functionally equivalent to KNL-1 because their inhibition, although preventing formation of a mechanically stable kinetochore-microtubule interface and causing chromosome missegregation, does not result in a kinetochore-null phenotype. The greater functional importance of KNL-1 may be due to its requirement for targeting multiple components of the outer kinetochore, including CeNDC-80 and HIM-10. Thus, KNL-1 plays a central role in translating the initiation of kinetochore assembly by CeCENP-A and CeCENP-C into the formation of a functional microtubule-binding interface.</jats:p>
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spelling Desai, Arshad Rybina, Sonja Müller-Reichert, Thomas Shevchenko, Andrej Shevchenko, Anna Hyman, Anthony Oegema, Karen 0890-9369 1549-5477 Cold Spring Harbor Laboratory Developmental Biology Genetics http://dx.doi.org/10.1101/gad.1126303 <jats:p>Segregation of the replicated genome during cell division requires kinetochores, mechanochemical organelles that assemble on mitotic chromosomes to connect them to spindle microtubules. CENP-A, a histone H3 variant, and CENP-C, a conserved structural protein, form the DNA-proximal foundation for kinetochore assembly. Using RNA interference-based genomics in <jats:italic>Caenorhabditis elegans</jats:italic>, we identified KNL-1, a novel kinetochore protein whose depletion, like that of CeCENP-A or CeCENP-C, leads to a “kinetochore-null” phenotype. KNL-1 is downstream of CeCENP-A and CeCENP-C in a linear assembly hierarchy. In embryonic extracts, KNL-1 exhibits substoichiometric interactions with CeCENP-C and forms a near-stoichiometric complex with CeNDC-80 and HIM-10, the <jats:italic>C. elegans</jats:italic> homologs of Ndc80p/HEC1p and Nuf2p—two widely conserved outer kinetochore components. However, CeNDC-80 and HIM-10 are not functionally equivalent to KNL-1 because their inhibition, although preventing formation of a mechanically stable kinetochore-microtubule interface and causing chromosome missegregation, does not result in a kinetochore-null phenotype. The greater functional importance of KNL-1 may be due to its requirement for targeting multiple components of the outer kinetochore, including CeNDC-80 and HIM-10. Thus, KNL-1 plays a central role in translating the initiation of kinetochore assembly by CeCENP-A and CeCENP-C into the formation of a functional microtubule-binding interface.</jats:p> KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in <i>C. elegans</i> Genes & Development
spellingShingle Desai, Arshad, Rybina, Sonja, Müller-Reichert, Thomas, Shevchenko, Andrej, Shevchenko, Anna, Hyman, Anthony, Oegema, Karen, Genes & Development, KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans, Developmental Biology, Genetics
title KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_full KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_fullStr KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_full_unstemmed KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_short KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
title_sort knl-1 directs assembly of the microtubule-binding interface of the kinetochore in <i>c. elegans</i>
title_unstemmed KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
topic Developmental Biology, Genetics
url http://dx.doi.org/10.1101/gad.1126303