Poly(ADP-ribose) is required for spindle assembly and structure

被引:187
作者
Chang, P [1 ]
Jacobson, MK
Mitchison, TJ
机构
[1] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA
[2] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA
[3] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85721 USA
关键词
D O I
10.1038/nature03061
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mitotic spindle is typically thought of as an array of microtubules, microtubule-associated proteins and motors that self-organizes to align and segregate chromosomes(1). The major spindle components consist of proteins and DNA, the primary structural elements of the spindle(1). Other macromolecules including RNA and lipids also associate with spindles, but their spindle function, if any, is unknown. Poly(ADP-ribose) ( PAR) is a large, branched, negatively charged polymeric macromolecule whose polymerization onto acceptor proteins is catalysed by a family of poly(ADP-ribose) polymerases (PARPs)(2). Several PARPs localize to the spindle in vertebrate cells, suggesting that PARPs and/or PAR have a role in spindle function(2). Here we show that PAR is enriched in the spindle and is required for spindle function-PAR hydrolysis or perturbation leads to rapid disruption of spindle structure, and hydrolysis during spindle assembly blocks the formation of bipolar spindles. PAR exhibits localization dynamics that differ from known spindle proteins and are consistent with a low rate of turnover in the spindle. Thus, PAR is a non-proteinaceous, non-chromosomal component of the spindle required for bipolar spindle assembly and function.
引用
收藏
页码:645 / 649
页数:5
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