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Lookup NU author(s): Dr Emma BriggsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
RNA-DNA hybrids are epigenetic features of all genomes that intersect with many processes, including transcription, telomere homeostasis, and centromere function. Increasing evidence suggests that RNA-DNA hybrids can provide two conflicting roles in the maintenance and transmission of genomes: They can be the triggers of DNA damage, leading to genome change, or can aid the DNA repair processes needed to respond to DNA lesions. Evasion of host immunity by African trypanosomes, such as Trypanosoma brucei, relies on targeted recombination of silent Variant Surface Glycoprotein (VSG) genes into a specialized telomeric locus that directs transcription of just one VSG from thousands. How such VSG recombination is targeted and initiated is unclear. Here, we show that a key enzyme of T. brucei homologous recombination, RAD51, interacts with RNA-DNA hybrids. In addition, we show that RNA-DNA hybrids display a genome-wide colocalization with DNA breaks and that this relationship is impaired by mutation of RAD51. Finally, we show that RAD51 acts to repair highly abundant, localised DNA breaks at the single transcribed VSG and that mutation of RAD51 alters RNA-DNA hybrid abundance at 70 bp repeats both around the transcribed VSG and across the silent VSG archive. This work reveals a widespread, generalised role for RNA-DNA hybrids in directing RAD51 activity during recombination and uncovers a specialised application of this interplay during targeted DNA break repair needed for the critical T. brucei immune evasion reaction of antigenic variation.
Author(s): Girasol MJ, Krasilnikova M, Marques CA, Damasceno JD, Lapsley C, Lemgruber L, Burchmore R, Beraldi D, Carruthers R, Briggs EM, McCulloch R
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences
Year: 2023
Volume: 120
Issue: 48
Print publication date: 28/11/2023
Online publication date: 21/11/2023
Acceptance date: 13/11/2023
Date deposited: 21/02/2025
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: https://doi.org/10.1073/pnas.2309306120
DOI: 10.1073/pnas.2309306120
Data Access Statement: Data, Materials, and Software Availability BLISS and DRIP-seq sequences are available at the NCBI Sequence Read Archive (SRA) under project number PRJEB61713 (119). Nanopore and Illumina reads used for genome assembly have been deposited to the NCBI SRA under project number PRJNA962304 (120). DRIP-MS data and availability is described Girasol et al., BIORXIV/2023/540366.
PubMed id: 37988471
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