Recent work has shown that R-loops exist at mitotic centromeres, but the function of these R-loops is not well understood. Here, we report that mitotic R-loops arise in distinct locations from those formed during interphase. They accumulate on chromosome arms in prophase, where they are quickly resolved and continue to be produced at repetitive sequences including centromeres during a mitotic stall. Aurora B kinase activity is required to resolve R-loops during prophase and R-loops promote the localization of the Chromosome Passenger Complex (CPC) to the inner centromere. CPC purified from mitotic chromosomes interacts with thirty-two proteins involved with R-loop biology. One of these, the RNA regulator RBMX, controls Aurora B localization and activity in vivo. Perturbations in R-loop homeostasis or RBMX cause defects in the maintenance of centromeric cohesion due to the mislocalization of the CPC. We conclude that R-loops are generated by mitotic processes in repetitive DNA sequences, they play important roles in mitotic fidelity, and we have identified a set of mitotic R-loop regulators including the CPC and RBMX that will enable future studies of mitotic R-loops.

中文翻译：

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有丝分裂R环指导Aurora B激酶保持着着丝粒的凝聚力

最近的工作表明，R环存在于有丝分裂的着丝粒上，但对这些R环的功能尚不十分了解。在这里，我们报告有丝分裂R环出现在与相间形成的位置不同的位置。它们在前期积累在染色体臂上，在那里它们很快被分解，并在有丝分裂失速期间以包括着丝粒的重复序列继续产生。需要极光B激酶活性来解决前期的R环，并且R环会促进染色体客体（CPC）定位到内部着丝粒。从有丝分裂染色体上纯化的CPC与32个参与R环生物学的蛋白质相互作用。其中之一，RNA调节剂RBMX，可控制Aurora B的定位和体内活性。由于CPC的定位错误，R环动态平衡或RBMX中的扰动会导致着丝粒凝聚力的维持出现缺陷。我们得出的结论是，R环是由重复的DNA序列中的有丝分裂过程产生的，它们在有丝分裂的保真度中起着重要的作用，并且我们确定了一套有丝分裂的R环调节剂，包括CPC和RBMX，这将使有丝分裂R-循环。