R-loops modulate Trypanosome antigenic variation

Diversity generation systems employed by microbes are usually termed antigenic variation systems, and while there are many mechanisms used to promote the expression of various different forms of a gene product, many organisms have co-opted DNA recombination and repair factors to mediate specialized...

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Bibliographic Details
Published in:PLoS genetics 2018-12, Vol.14 (12), p.e1007809-e1007809
Main Authors: Prister, Lauren L, Seifert, H Steven
Format: Article
Language:English
Subjects:
African trypanosomiasis
Amyotrophic lateral sclerosis
Antigenic Variation
Antigens, Surface
Biodiversity
Biology and Life Sciences
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
DNA-directed RNA polymerase
Enzymes
Gene conversion
Genes
Genetic aspects
Genetic variation
Genomes
Glycoproteins
Immune Evasion
Immunoglobulins
Immunology
Medicine and Health Sciences
Mutation
R-loops
Recombination
Research and analysis methods
Ribonuclease H
RNA polymerase
Transcription activation
Trypanosoma
Trypanosoma - immunology
Trypanosoma brucei
Variant surface glycoprotein
Variant Surface Glycoproteins, Trypanosoma - genetics
Variation
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Summary:Diversity generation systems employed by microbes are usually termed antigenic variation systems, and while there are many mechanisms used to promote the expression of various different forms of a gene product, many organisms have co-opted DNA recombination and repair factors to mediate specialized gene conversion reactions [1]. Trypanosoma brucei is the causative agent of African sleeping sickness and has one of the most well-studied antigenic variation systems that can produce thousands of versions of the variable surface glycoprotein (VSG) for immune avoidance. The second model proposes that R-loops trigger the transcriptional activation of silent telomeric VSGs through a shared direct mechanism, involving DNA damage or an unknown, indirect mechanism. Since Briggs and colleagues have not directly shown what sort of damage occurs (e.g., base changes, replication stalls, or interrupted repair processes), they have not directly linked the increased γ-H2A levels to the antigenic variation process. RNA polymerase I transcribes procyclin genes and variant surface glycoprotein gene expression sites in Trypanosoma brucei.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1007809