Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment

Cdt1, a protein critical for replication origin licensing in G1 phase is degraded during S phase but re-accumulates in G2 phase. We now demonstrate that human Cdt1 has a separable essential mitotic function. Cdt1 localizes to kinetochores during mitosis through interaction with the Hec1 component of...

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Hauptverfasser: Varma, Dileep, Chandrasekaran, Srikripa, Sundin, Lynsie J. R., Reidy, Karen T., Wan, Xiaohu, Chasse, Dawn A. D., Nevis, Kathleen R., DeLuca, Jennifer G., Salmon, E. D., Cook, Jeanette Gowen
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Sprache:Inglês
Veröffentlicht: 2012
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Online Zugang:https://ncbi.nlm.nih.gov/pmc/articles/PMC3366049/
https://ncbi.nlm.nih.gov/pubmed/22581055
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1038/ncb2489
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spelling pubmed-33660492012-12-01 Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment Varma, Dileep Chandrasekaran, Srikripa Sundin, Lynsie J. R. Reidy, Karen T. Wan, Xiaohu Chasse, Dawn A. D. Nevis, Kathleen R. DeLuca, Jennifer G. Salmon, E. D. Cook, Jeanette Gowen Nat Cell Biol Article Cdt1, a protein critical for replication origin licensing in G1 phase is degraded during S phase but re-accumulates in G2 phase. We now demonstrate that human Cdt1 has a separable essential mitotic function. Cdt1 localizes to kinetochores during mitosis through interaction with the Hec1 component of the Ndc80 complex. G2-specific depletion of Cdt1 arrests cells in late prometaphase due to abnormally unstable kinetochore-microtubule (kMT) attachments and Mad1-dependent spindle assembly checkpoint activity. Cdt1 binds a unique loop extending from the rod domain of Hec1 that we show is also required for kMT attachment. Mutation of the loop domain prevents Cdt1 kinetochore localization and arrests cells in prometaphase. Super-resolution fluorescence microscopy indicates that Cdt1 binding to the Hec1 loop domain promotes a microtubule-dependent conformational change in the Ndc80 complex in vivo. These results support the conclusion that Cdt1 binding to Hec1 is essential for an extended Ndc80 configuration and stable kinetochore microtubule attachment. 2012-05-13 /pmc/articles/PMC3366049/ /pubmed/22581055 http://dx.doi.org/10.1038/ncb2489 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Article
spellingShingle Article
Varma, Dileep
Chandrasekaran, Srikripa
Sundin, Lynsie J. R.
Reidy, Karen T.
Wan, Xiaohu
Chasse, Dawn A. D.
Nevis, Kathleen R.
DeLuca, Jennifer G.
Salmon, E. D.
Cook, Jeanette Gowen
Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment
description Cdt1, a protein critical for replication origin licensing in G1 phase is degraded during S phase but re-accumulates in G2 phase. We now demonstrate that human Cdt1 has a separable essential mitotic function. Cdt1 localizes to kinetochores during mitosis through interaction with the Hec1 component of the Ndc80 complex. G2-specific depletion of Cdt1 arrests cells in late prometaphase due to abnormally unstable kinetochore-microtubule (kMT) attachments and Mad1-dependent spindle assembly checkpoint activity. Cdt1 binds a unique loop extending from the rod domain of Hec1 that we show is also required for kMT attachment. Mutation of the loop domain prevents Cdt1 kinetochore localization and arrests cells in prometaphase. Super-resolution fluorescence microscopy indicates that Cdt1 binding to the Hec1 loop domain promotes a microtubule-dependent conformational change in the Ndc80 complex in vivo. These results support the conclusion that Cdt1 binding to Hec1 is essential for an extended Ndc80 configuration and stable kinetochore microtubule attachment.
author Varma, Dileep
Chandrasekaran, Srikripa
Sundin, Lynsie J. R.
Reidy, Karen T.
Wan, Xiaohu
Chasse, Dawn A. D.
Nevis, Kathleen R.
DeLuca, Jennifer G.
Salmon, E. D.
Cook, Jeanette Gowen
author_facet Varma, Dileep
Chandrasekaran, Srikripa
Sundin, Lynsie J. R.
Reidy, Karen T.
Wan, Xiaohu
Chasse, Dawn A. D.
Nevis, Kathleen R.
DeLuca, Jennifer G.
Salmon, E. D.
Cook, Jeanette Gowen
author_sort Varma, Dileep
title Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment
title_short Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment
title_full Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment
title_fullStr Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment
title_full_unstemmed Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore microtubule attachment
title_sort recruitment of the human cdt1 replication licensing protein by the loop domain of hec1 is required for stable kinetochore microtubule attachment
publishDate 2012
url https://ncbi.nlm.nih.gov/pmc/articles/PMC3366049/
https://ncbi.nlm.nih.gov/pubmed/22581055
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1038/ncb2489
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