TbRAP1 has an unusual duplex DNA binding activity required for its telomere localization and VSG silencing

Marjia Afrin, Amit Kumar Gaurav, Xian Yang, Xuehua Pan, Yanxiang Zhao (Corresponding Author), Bibo Li

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

Localization of Repressor Activator Protein 1 (RAP1) to the telomere is essential for its telomeric functions. RAP1 homologs either directly bind the duplex telomere DNA or interact with telomere-binding proteins. We find that Trypanosoma brucei RAP1 relies on a unique double-stranded DNA (dsDNA) binding activity to achieve this goal. T. brucei causes human sleeping sickness and regularly switches its major surface antigen, variant surface glycoprotein (VSG), to evade the host immune response. VSGs are monoallelically expressed from subtelomeres, and TbRAP1 is essential for VSG regulation. We identify dsDNA and single-stranded DNA binding activities in TbRAP1, which require positively charged 737RKRRR741 residues that overlap with TbRAP1's nuclear localization signal in the MybLike domain. Both DNA binding activities are electrostatics-based and sequence nonspecific. The dsDNA binding activity can be substantially diminished by phosphorylation of two 737RKRRR741-adjacent S residues and is essential for TbRAP1's telomere localization, VSG silencing, telomere integrity, and cell proliferation.

Original languageEnglish
Article numbereabc4065
JournalScience advances
Volume6
Issue number38
DOIs
Publication statusPublished - Sep 2020

ASJC Scopus subject areas

  • General

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