Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation

Andrea Zurita Leal, Marie Schwebs, Emma Briggs, Nadine Weisert, Helena Reis, Leandro Lemgruber, Katarina Luko, Jonathan Wilkes, Falk Butter, Richard McCulloch, Christian J Janzen

Research output: Contribution to journalArticlepeer-review

Abstract

Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to offspring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.

Original languageEnglish
Pages (from-to)9660-9680
Number of pages21
JournalNucleic Acids Research
Volume48
Issue number17
DOIs
Publication statusPublished - 5 Sep 2020

Keywords

  • antigenic variation
  • cell line
  • cell nucleus
  • Chromosome Segregation
  • DNA replication
  • DNA-directed DNA polymerase
  • Gene Expression Regulation
  • Genome, Protozoan
  • Humans
  • Protozoan Proteins/genetics
  • RNA Interference
  • Telomere/genetics
  • Trypanosoma brucei brucei/genetics
  • Variant Surface Glycoproteins, Trypanosoma/genetics
  • enzymology
  • genetics

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