The conserved Rap1 protein is part of the shelterin complex that plays critical roles in chromosome end protection and telomere length regulation. Previous studies have addressed how fission yeast Rap1 contributes to telomere length maintenance, but the mechanism by which the protein inhibits end fusions has remained elusive. Here, we use a mutagenesis screen in combination with high-throughput sequencing to identify several amino acid positions in Rap1 that have key roles in end protection. Interestingly, mutations at these sites render cells susceptible to genome instability in a conditional manner, whereby longer telomeres are prone to undergoing end fusions, while telomeres within the normal length range are sufficiently protected. The protection of long telomeres is in part dependent on their nuclear envelope attachment mediated by the Rap1–Bqt4 interaction. Our data demonstrate that long telomeres represent a challenge for the maintenance of genome integrity, thereby providing an explanation for species-specific upper limits on telomere length.

中文翻译：

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Rap1 阻止裂变酵母中长端粒之间的融合

保守的Rap1 蛋白是shelterin 复合物的一部分，在染色体末端保护和端粒长度调节中起关键作用。以前的研究已经解决了裂变酵母 Rap1 如何有助于维持端粒长度，但蛋白质抑制末端融合的机制仍然难以捉摸。在这里，我们使用诱变筛选结合高通量测序来识别 Rap1 中在末端保护中起关键作用的几个氨基酸位置。有趣的是，这些位点的突变使细胞在有条件的情况下易受基因组不稳定的影响，从而较长的端粒容易发生末端融合，而正常长度范围内的端粒则受到充分保护。长端粒的保护部分依赖于由 Rap1-Bqt4 相互作用介导的核膜附着。我们的数据表明，长端粒代表了维持基因组完整性的挑战，从而为特定物种的端粒长度上限提供了解释。