TOPO3alpha influences antigenic variation by monitoring expression-site-associated VSG switching in Trypanosoma brucei.

PLoS Pathogens
Hee-Sook Kim, George A M Cross

Abstract

Homologous recombination (HR) mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein (VSG) gene under the control of the active expression site (ES). It is believed that the majority of VSG switching events occur by duplicative gene conversion, but only a few DNA repair genes that are central to HR have been assigned a role in this process. Gene conversion events that are associated with crossover are rarely seen in VSG switching, similar to mitotic HR. In other organisms, TOPO3alpha (Top3 in yeasts), a type IA topoisomerase, is part of a complex that is involved in the suppression of crossovers. We therefore asked whether a related mechanism might suppress VSG recombination. Using a set of reliable recombination and switching assays that could score individual switching mechanisms, we discovered that TOPO3alpha function is conserved in Trypanosoma brucei and that TOPO3alpha plays a critical role in antigenic switching. Switching frequency increased 10-40-fold in the absence of TOPO3alpha and this hyper-switching phenotype required RAD51. Moreover, the preference of 70-bp repeats for VSG recombination was mitigated, while homology regions elsewhere in ES were ...Continue Reading

References

Jan 1, 1987·Molecular and Cellular Biology·M G Lee, L H Van der Ploeg
Sep 15, 1988·Gene·J M KooterP Borst
Mar 5, 1987·Journal of Molecular Biology·H T TimmersP Borst
Apr 5, 1985·Journal of Molecular Biology·A Y LiuP Borst
Dec 10, 1983·Nucleic Acids Research·T De LangeP Borst
Jul 12, 1996·The Journal of Biological Chemistry·K OhshimaR D Wells
Jun 1, 1997·Molecular and Biochemical Parasitology·K P DaviesG A Cross
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·W Li, J C Wang
Aug 24, 1999·Molecular and Cellular Biology·N P RobinsonJ D Barry
Mar 7, 2001·Current Biology : CB·P HuangE J Louis
May 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·K Y Kwan, J C Wang
Jun 8, 2001·Annual Review of Biochemistry·J J Champoux
Oct 5, 2001·Molecular and Cellular Biology·R K ChakravertyI D Hickson
Oct 20, 2001·Genes & Development·V KaliramanS J Brill
Feb 13, 2002·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Alan H Fairlamb
May 4, 2002·Nature Reviews. Molecular Cell Biology·Damien D'Amours, Stephen P Jackson
May 16, 2002·The Journal of Biological Chemistry·Nicholas P RobinsonJ David Barry
Sep 14, 2002·Current Genetics·Vivek Kaliraman, Steven J Brill
May 2, 2003·Molecular and Cellular Biology·Suzanne A Bastin-ShanowerSteven J Brill

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Citations

Dec 18, 2014·International Journal for Parasitology. Drugs and Drug Resistance·Rafael Balaña-FouceRosa M Reguera
Oct 23, 2010·Nucleic Acids Research·Lucy GloverDavid Horn
Jul 8, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Keith R MatthewsLiam J Morrison
Jan 4, 2012·FEMS Microbiology Reviews·Cornelis VinkH Steven Seifert
Mar 7, 2014·Microbiology and Molecular Biology Reviews : MMBR·Marie-Michelle GenoisJean-Yves Masson
Jan 23, 2016·PLoS Genetics·Danae SchulzHee-Sook Kim
Sep 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Francisco Aresta-BrancoLuisa M Figueiredo
May 19, 2018·Current Medicinal Chemistry·Rosa M RegueraRafael Balaña-Fouce
May 28, 2011·Molecular Microbiology·Rachel DobsonRichard McCulloch
Nov 5, 2019·Journal of Molecular Biology·Arpita SahaBibo Li
Jan 7, 2021·Microorganisms·Ahmed SeddekYuk-Ching Tse-Dinh
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Héllida Marina Costa-SilvaCarlos Renato Machado
Jun 25, 2015·Microbiology Spectrum·Richard McCullochJames P J Hall

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Methods Mentioned

BETA
PCR
transfection
electrophoresis
genotyping

Software Mentioned

SMART ( Simple Modular Architecture Research Tool )
TOPO3α

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