Document Detail


RNAi analysis reveals an unexpected role for topoisomerase II in chromosome arm congression to a metaphase plate.
MedLine Citation:
PMID:  14600258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA topoisomerase II (Topo II) is a major component of mitotic chromosomes and an important drug target in cancer chemotherapy, however, its role in chromosome structure and dynamics remains controversial. We have used RNAi to deplete Topo II in Drosophila S2 cells in order to carry out a detailed functional analysis of the role of the protein during mitosis. We find that Topo II is not required for the assembly of a functional kinetochore or the targeting of chromosomal passenger proteins, nonetheless, it is essential for anaphase sister chromatid separation. In response to a long-running controversy, we show that Topo II does have some role in mitotic chromatin condensation. Chromosomes formed in its absence have a 2.5-fold decrease in the level of chromatin compaction, and are morphologically abnormal. However, it is clear that the overall programme of mitotic chromosome condensation can proceed without Topo II. Surprisingly, in metaphase cells depleted of Topo II, one or more chromosome arms frequently stretch out from the metaphase plate to the vicinity of the spindle pole. This is not kinetochore-based movement, as the centromere of the affected chromosome is located on the plate. This observation raises the possibility that further unexpected functions for Topo II may remain to be discovered.
Authors:
Chih-Jui Chang; Sarah Goulding; William C Earnshaw; Mar Carmena
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cell science     Volume:  116     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-05     Completed Date:  2004-06-09     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  4715-26     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anaphase / physiology*
Animals
Cell Division
Chromatin / metabolism
DNA Topoisomerases, Type II / metabolism*
Drosophila / metabolism
Histones / metabolism
Kinetochores / metabolism*
Metaphase / physiology*
Microscopy, Fluorescence
Phosphorylation
RNA, Small Interfering / metabolism*
Spindle Apparatus / metabolism
Topoisomerase II Inhibitors
Grant Support
ID/Acronym/Agency:
073915//Wellcome Trust
Chemical
Reg. No./Substance:
0/Chromatin; 0/Histones; 0/RNA, Small Interfering; 0/Topoisomerase II Inhibitors; EC 5.99.1.3/DNA Topoisomerases, Type II

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