Telomerase-free cancer cells employ a recombination-based alternative lengthening of telomeres (ALT) pathway that depends on ALT-associated promyelocytic leukemia nuclear bodies (APBs), whose function is unclear. We find that APBs behave as liquid condensates in response to telomere DNA damage, suggesting two potential functions: condensation to enrich DNA repair factors and coalescence to cluster telomeres. To test these models, we developed a chemically induced dimerization approach to induce de novo APB condensation in live cells without DNA damage. We show that telomere-binding protein sumoylation nucleates APB condensation via interactions between small ubiquitin-like modifier (SUMO) and SUMO interaction motif (SIM), and that APB coalescence drives telomere clustering. The induced APBs lack DNA repair factors, indicating that APB functions in promoting telomere clustering can be uncoupled from enriching DNA repair factors. Indeed, telomere clustering relies only on liquid properties of the condensate, as an alternative condensation chemistry also induces clustering independent of sumoylation. Our findings introduce a chemical dimerization approach to manipulate phase separation and demonstrate how the material properties and chemical composition of APBs independently contribute to ALT, suggesting a general framework for how chromatin condensates promote cellular functions.

不含端粒酶的癌细胞采用基于重组的端粒（ALT）途径替代性延长途径，该途径取决于ALT相关的早幼粒细胞白血病核体（APB），其功能尚不清楚。我们发现，APBs响应端粒DNA损伤而表现为液体冷凝物，提示两个潜在功能：浓缩以丰富DNA修复因子和聚结成簇的端粒。为了测试这些模型，我们开发了一种化学诱导的二聚化方法，可以在没有DNA损伤的情况下在活细胞中诱导从头进行APB缩合。我们显示，端粒结合蛋白sumoylation通过小泛素样修饰剂（SUMO）和SUMO相互作用基序（SIM）之间的相互作用来成核APB缩合，并且APB合并驱动端粒聚类。诱导的APB缺乏DNA修复因子，表明APB在促进端粒聚集中的功能可以与丰富的DNA修复因子脱钩。的确，端粒簇仅依赖于冷凝物的液体性质，因为另一种缩合化学也可引起与磺酰化反应无关的簇。我们的发现引入了一种化学二聚化方法来控制相分离，并证明了APB的材料特性和化学成分如何独立地促进ALT，这为染色质浓缩物如何促进细胞功能提供了一个通用框架。