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Loss of TOP3B leads to increased R-loop formation and genome instability


Zhang, T and Wallis, M and Petrovic, V and Challis, J and Kalitsis, P and Hudson, DF, Loss of TOP3B leads to increased R-loop formation and genome instability, Open Biology, 9, (12) Article 190222. ISSN 2046-2441 (2019) [Refereed Article]


Copyright Statement

Copyright 2019 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1098/rsob.190222


Topoisomerase III beta (TOP3B) is one of the least understood members of the topoisomerase family of proteins and remains enigmatic. Our recent data shed light on the function and relevance of TOP3B to disease. A homozygous deletion for the TOP3B gene was identified in a patient with bilateral renal cancer. Analyses in both patient and modelled human cells show the disruption of TOP3B causes genome instability with a rise in DNA damage and chromosome bridging (mis-segregation). The primary molecular defect underlying this pathology is a significant increase in R-loop formation. Our data show that TOP3B is necessary to prevent the accumulation of excessive R-loops and identify TOP3B as a putative cancer gene, and support recent data showing that R-loops are involved in cancer aetiology.

Item Details

Item Type:Refereed Article
Keywords:R-loop, TOP3B, genomic instability, topoisomerase
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genomics
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Wallis, M (Dr Mathew Wallis)
ID Code:137265
Year Published:2019
Web of Science® Times Cited:29
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-02-06
Last Modified:2020-03-30
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