Loss of TOP3B leads to increased R-loop formation and genome instability
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2019-12-01
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| Series: | Open Biology |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.190222 |
| _version_ | 1818939009049559040 |
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| author | Tao Zhang Mathew Wallis Vida Petrovic Jackie Challis Paul Kalitsis Damien F. Hudson |
| author_facet | Tao Zhang Mathew Wallis Vida Petrovic Jackie Challis Paul Kalitsis Damien F. Hudson |
| author_sort | Tao Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T06:16:56Z |
| format | Article |
| id | doaj.art-0c774b2dce174478a6b8d963cc8daa9b |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-20T06:16:56Z |
| publishDate | 2019-12-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-0c774b2dce174478a6b8d963cc8daa9b2022-12-21T19:50:30ZengThe Royal SocietyOpen Biology2046-24412019-12-0191210.1098/rsob.190222190222Loss of TOP3B leads to increased R-loop formation and genome instabilityTao ZhangMathew WallisVida PetrovicJackie ChallisPaul KalitsisDamien F. HudsonTopoisomerase 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.190222topoisomerasetop3br-loopgenomic instability |
| spellingShingle | Tao Zhang Mathew Wallis Vida Petrovic Jackie Challis Paul Kalitsis Damien F. Hudson Loss of TOP3B leads to increased R-loop formation and genome instability Open Biology topoisomerase top3b r-loop genomic instability |
| title | Loss of TOP3B leads to increased R-loop formation and genome instability |
| title_full | Loss of TOP3B leads to increased R-loop formation and genome instability |
| title_fullStr | Loss of TOP3B leads to increased R-loop formation and genome instability |
| title_full_unstemmed | Loss of TOP3B leads to increased R-loop formation and genome instability |
| title_short | Loss of TOP3B leads to increased R-loop formation and genome instability |
| title_sort | loss of top3b leads to increased r loop formation and genome instability |
| topic | topoisomerase top3b r-loop genomic instability |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.190222 |
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