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Title: | TbRAP1 has an unusual duplex DNA binding activity required for its telomere localization and VSG silencing | Authors: | Afrin, M Gaurav, AK Yang, X Pan, XH Zhao, YX Li, BB |
Issue Date: | 18-Sep-2020 | Source: | Science advances, 18 Sept. 2020, v. 6, no. 38, eabc4065, p. 1-12 | 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. | Publisher: | American Association for the Advancement of Science (AAAS) | Journal: | Science advances | ISSN: | 2375-2548 | DOI: | 10.1126/sciadv.abc4065 | Rights: | Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). The following publication M. Afrin, A. K. Gaurav, X. Yang, X. Pan, Y. Zhao, B. Li, TbRAP1 has an unusual duplex DNA binding activity required for its telomere localization and VSG silencing. Sci. Adv. 6, eabc4065 (2020) is available at https://dx.doi.org/10.1126/sciadv.abc4065 |
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