TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution.
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Date
2015-03-12ICR Author
Author
Broderick, R
Nieminuszczy, J
Blackford, AN
Winczura, A
Niedzwiedz, W
Type
Journal Article
Metadata
Show full item recordAbstract
During mitosis, sister chromatids must be faithfully segregated to ensure that daughter cells receive one copy of each chromosome. However, following replication they often remain entangled. Topoisomerase IIα (TOP2A) has been proposed to resolve such entanglements, but the mechanisms governing TOP2A recruitment to these structures remain poorly understood. Here, we identify TOPBP1 as a novel interactor of TOP2A, and reveal that it is required for TOP2A recruitment to ultra-fine anaphase bridges (UFBs) in mitosis. The C-terminal region of TOPBP1 interacts with TOP2A, and TOPBP1 recruitment to UFBs requires its BRCT domain 5. Depletion of TOPBP1 leads to accumulation of UFBs, the majority of which arise from centromeric loci. Accordingly, expression of a TOPBP1 mutant that is defective in TOP2A binding phenocopies TOP2A depletion. These findings provide new mechanistic insights into how TOP2A promotes resolution of UFBs during mitosis, and highlights a pivotal role for TOPBP1 in this process.
Collections
Subject
Cell Line, Tumor
Hela Cells
Chromosomes
Centromere
Chromatids
Humans
DNA Topoisomerases, Type II
Carrier Proteins
Cell Cycle Proteins
DNA-Binding Proteins
Green Fluorescent Proteins
Nuclear Proteins
DNA
Antigens, Neoplasm
Microscopy, Fluorescence
Anaphase
Mitosis
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
Protein Structure, Tertiary
Protein Binding
Mutation
HEK293 Cells
Poly-ADP-Ribose Binding Proteins
Research team
Cancer and Genome Instability
Language
eng
Date accepted
2015-02-09
License start date
2015-03-12
Citation
Nature communications, 2015, 6 pp. 6572 - ?
Publisher
NATURE PUBLISHING GROUP
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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