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Dr.Hideki Yokoyama (ZMBH) New mitotic regulators released from chromatin

Dr.Hideki Yokoyama (ZMBH) New mitotic regulators released from chromatin

New mitotic regulators released from chromatin

2013.08.26 15:51
16:00-
片平・生命科学プロジェクト研究棟 1階講義室A
Dr. Hideki Yokoyama
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH),
DKFZ-ZMBH Alliance , Heidelberg, Germany
生命科学研究科発生ダイナミクス分野 杉本亜砂子
e-mail:asugimoto*m.tohoku.ac.jp(*を@に置き換えてください)
電話:022-217-6194
In mitosis, chromosomes are more than passive passengers 
segregated by spindle microtubules. They actively drive s
pindle ass embly by producing the GTP bound form of the 
RanGTPase in their vicinity. Ran-GTP binds to the 
heterodimeric nuclear transport receptor importin α/β and 
dissociates nuclear localization signal (NLS)-containing 
proteins from the importins. Liberated NLS proteins, such 
as TPX2, play distinct roles in spindle microtubule assembly. 

To comprehensively identify novel Ran-regulated spindle 
assembly factors, I sequentially purified NLS proteins and 
microtubule-associated proteins (MAPs) from Xenopus egg 
extracts, and identified ~150 proteins (Yokoyama et al., 2009).
Of those, the chromatin-remodeling ATPases, CHD4 and ISWI, 
surprisingly function as bona-fide MAPs in vitro. Both proteins 
dissociate from chromatin in mitosis and re-localize to the 
spindle. Their mitotic functions are, however, temporally 
distinct: CHD4 is a Ran-GTP dependent microtubule stabilizer 
essential for spindle assembly (Yokoyama et al., in press), 
while ISWI specifically stabilizes microtubules in anaphase to 
maintain the spindle and ensure chromosome segregation 
(Yokoyama et al., 2009). The functions of CHD4 and ISWI are 
independent of chromatin remodeling, and are conserved in 
Xenopus egg extracts and human cells. 

My data establish a new principle that chromosomes drive not 
only spindle assembly but also other mitotic processes 
essential for their own segregation. The direct function of 
chromosomes is to produce Ran-GTP and additionally to release 
important mitotic regulators from them.