Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7572
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Funding
- Worldwide Cancer Research International Fellowship
- WIMM/Medical Research Council Senior Non Clinical Fellowship
- Polish Ministry of Science and Higher Education fellowship
- Polish National Science Center grant [N303 571539]
- Cancer Research UK [11224] Funding Source: researchfish
- Medical Research Council [MR/K01577X/1, G0902418] Funding Source: researchfish
- Wellcome Trust [107457/Z/15/Z] Funding Source: researchfish
- Worldwide Cancer Research [07-0922] Funding Source: researchfish
- MRC [MR/K01577X/1, G0902418] Funding Source: UKRI
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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 Il alpha (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.
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