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

Nature Cell Biology
Dileep VarmaJeanette Gowen Cook

Abstract

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 owing 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 kMT attachment.

References

Jul 11, 1998·Cell·T J McGarry, M W Kirschner
Aug 12, 1998·The Journal of Cell Biology·D A StarrM L Goldberg
Apr 18, 2000·The Journal of Cell Biology·H LeonhardtM C Cardoso
Dec 23, 2000·Science·J A WohlschlegelA Dutta
Feb 19, 2002·Oncogene·Elizabeth ArentsonKyunghee Choi
Aug 10, 2002·Science·Supriya G PrasanthBruce Stillman
Jan 30, 2003·The EMBO Journal·Lorena Clay-FarraceRonald A Laskey
May 10, 2003·The Journal of Biological Chemistry·Michael J FitchBik K Tye
Dec 16, 2003·The Journal of Biological Chemistry·Jeanette Gowen CookJoseph R Nevins
Jul 9, 2004·Developmental Cell·Patrick MeraldiPeter K Sorger
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Marylynn SnyderJ Jillian Zhang
Feb 17, 2006·The EMBO Journal·Hideo NishitaniTakeharu Nishimoto
Jan 2, 2007·Nature Structural & Molecular Biology·Ronnie R WeiStephen C Harrison
Jul 17, 2007·Annual Review of Genetics·R A Sclafani, T M Holzen
Nov 17, 2007·Genes & Development·Shuyan ChenStephen P Bell
Nov 17, 2007·Cancer Research·Michalis LiontosVassilis G Gorgoulis
Sep 24, 2008·The Journal of Cell Biology·Dileep VarmaRichard B Vallee
Nov 26, 2008·Current Biology : CB·Stephanie A MillerP Todd Stukenberg
Nov 26, 2008·Current Biology : CB·Geoffrey J GuimaraesJennifer G Deluca
May 15, 2009·Cell Cycle·Kathleen R NevisJeanette Gowen Cook
Jan 6, 2010·Journal of Cell Science·Kazumasa YoshidaMasatoshi Fujita
Oct 15, 2010·Nature·Gregory M AlushinEva Nogales
Jan 25, 2011·Current Biology : CB·Jean-François MaureTomoyuki U Tanaka
Mar 23, 2011·The Journal of Cell Biology·Juan A Bernal, Ashok R Venkitaraman
Sep 21, 2011·Molecular and Cellular Biology·Srikripa ChandrasekaranJeanette Gowen Cook

❮ Previous
Next ❯

Citations

Dec 22, 2012·Nature Reviews. Molecular Cell Biology·Emily A Foley, Tarun M Kapoor
Jul 10, 2013·Proceedings of the National Academy of Sciences of the United States of America·Andrea BallabeniMarc W Kirschner
Sep 26, 2013·The Journal of Biological Chemistry·Christophe CaillatAnastassis Perrakis
Sep 22, 2012·Journal of Biochemistry·Kozo Tanaka
Mar 19, 2013·Cell Division·Ngang Heok Tang, Takashi Toda
Feb 19, 2013·Journal of Cell Science·Dileep Varma, E D Salmon
Feb 22, 2013·Molecular Biology of the Cell·Ngang Heok TangTakashi Toda
Jul 3, 2013·Cold Spring Harbor Perspectives in Biology·Michael O'DonnellBruce Stillman
Nov 17, 2012·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jakob Nilsson
Jan 6, 2015·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Ngang Heok Tang, Takashi Toda
Feb 18, 2014·Current Opinion in Cell Biology·Dhanya K Cheerambathur, Arshad Desai
Mar 29, 2014·FEMS Microbiology Reviews·Yuya YamagishiYoshinori Watanabe
Jun 9, 2015·Nature Cell Biology·Pavithra AravamudhanAjit P Joglekar
Apr 30, 2014·Cell Cycle·Yanchang WangKelly McKnight
Jul 31, 2013·Current Biology : CB·Roshan L Shrestha, Viji M Draviam
Feb 25, 2015·Biochemical and Biophysical Research Communications·Ya-Lan FengJun Yin
Aug 6, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Linda Truebestein, Thomas A Leonard
Feb 8, 2018·Chromosoma·Nicolaas C Baudoin, Daniela Cimini
Jan 24, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Qian ZhangHong Liu
Nov 18, 2017·ELife·Jacob Peter MatsonJeanette Gowen Cook
Jun 16, 2017·Endocrine-related Cancer·Shivangi Agarwal, Dileep Varma
May 31, 2012·Nature Cell Biology·Daniel R Matson, P Todd Stukenberg
Sep 27, 2019·FEBS Letters·Juanita C Limas, Jeanette Gowen Cook
Aug 26, 2020·PLoS Genetics·Yizhuo ZhouJeanette Gowen Cook
Aug 3, 2013·Cold Spring Harbor Protocols·Scott K LyonsKevin M Brindle
Feb 10, 2018·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kohei NukinaHideo Nishitani
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Haipeng Liu, Constance J Jeffery
Jun 23, 2020·Biochemistry. Biokhimii︠a︡·N B UstinovN B Gudimchuk
Nov 21, 2014·The Journal of Biological Chemistry·Lindsay F RizzardiJeanette Gowen Cook
Jan 17, 2020·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Idun D ReinTrond Stokke
Mar 13, 2020·Frontiers in Cell and Developmental Biology·Robert T Wimbish, Jennifer G DeLuca
Aug 28, 2020·Essays in Biochemistry·Amit RahiDileep Varma
Aug 30, 2018·The Journal of Cell Biology·Shivangi AgarwalDileep Varma
Dec 7, 2020·Cytoskeleton·Joseph Y OngJorge Z Torres

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
two-hybrid
co-immunoprecipitation
fluorescence microscopy
confocal microscopy
co-immunoprecipitations

Software Mentioned

Adobe Photoshop

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.