Document Type

Article

Publication Date

9-2020

Publication Title

Science Advances

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.

Comments

This work is supported by an NIH R01 grant AI066095 (PI, to B.L.), an NIH S10 grant S10OD025252 (PI, to B.L.), a Research Grants Council GRF grant PolyU 151062/18M (PI, to Y.Z.), and a Research Grants Council AoE grant AoE/M-09/12 (PI, to Y.Z.). The publication cost is partly supported by GRHD at CSU.

DOI

10.1126/sciadv.abc4065

Version

Publisher's PDF

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Volume

6

Issue

38

Included in

Biology Commons

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