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KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans
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Zeitschriftentitel: | Genes & Development |
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Personen und Körperschaften: | , , , , , , |
In: | Genes & Development, 17, 2003, 19, S. 2421-2435 |
Format: | E-Article |
Sprache: | Englisch |
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Cold Spring Harbor Laboratory
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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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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 |
doi_str_mv |
10.1101/gad.1126303 |
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Online Free |
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Biologie |
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ElectronicArticle |
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DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-D161 DE-Zwi2 |
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Cold Spring Harbor Laboratory, 2003 |
imprint_str_mv |
Cold Spring Harbor Laboratory, 2003 |
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0890-9369 1549-5477 |
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0890-9369 1549-5477 |
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2003 |
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Cold Spring Harbor Laboratory |
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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 |
author_sort | desai, arshad |
container_issue | 19 |
container_start_page | 2421 |
container_title | Genes & Development |
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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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institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Zwi2 |
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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 |