DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement.

The Journal of Cell Biology
Chang-Young JangG Fang

Abstract

Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases.

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Citations

Feb 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yifat Merbl, Marc W Kirschner
Nov 27, 2009·The Journal of Biological Chemistry·Guorong LiPedro Gonzalez
Apr 9, 2009·Journal of Cell Science·Chang-Young JangGuowei Fang
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Jan 23, 2016·Biochemical and Biophysical Research Communications·Ji Eun ParkChang-Young Jang
Jan 29, 2016·Biochemical and Biophysical Research Communications·Seul Kim, Chang-Young Jang
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Mar 24, 2011·Biochemical and Biophysical Research Communications·Chang-Young Jang, Guowei Fang
Feb 2, 2010·Biochemical and Biophysical Research Communications·Chang-Young JangGuowei Fang
Apr 9, 2011·Biochemical and Biophysical Research Communications·Chang-Young JangGuowei Fang
Mar 5, 2015·Journal of Cellular Biochemistry·Jin-Ju KimHyuk-Jin Cha
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Methods Mentioned

BETA
transfection
FACS
immunoprecipitation
two-hybrid

Software Mentioned

DTASelect
SEQUEST
AutoVisualizer
Openlab
AutoDeblur

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