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.

阻遏激活蛋白 1 (RAP1) 对端粒的定位对其端粒功能至关重要。RAP1 同源物要么直接结合双链体端粒 DNA，要么与端粒结合蛋白相互作用。我们发现布氏锥虫RAP1 依赖于独特的双链 DNA (dsDNA) 结合活性来实现这一目标。T. brucei引起人类昏睡病并定期转换其主要表面抗原变异表面糖蛋白 (VSG) 以逃避宿主免疫反应。VSGs 从亚端粒单等位基因表达，Tb RAP1 对 VSG 调节至关重要。我们鉴定了Tb RAP1中的 dsDNA 和单链 DNA 结合活性，这需要带正电荷的₇₃₇ RKRRR在 MybLike 域中与Tb RAP1 的核定位信号重叠的_{741个残基。}两种 DNA 结合活动都是基于静电的且序列非特异性的。dsDNA 结合活性可以通过磷酸化两个₇₃₇ RKRRR ₇₄₁相邻的S 残基而大大降低，并且对于Tb RAP1 的端粒定位、VSG 沉默、端粒完整性和细胞增殖至关重要。