Homologous recombination (HR) is a key process for repairing DNA double strand breaks and for promoting genetic diversity. However, HR occurs unevenly across the genome, and certain genomic features can influence its activity. One such feature is the presence of guanine quadruplexes (G4s), stable secondary structures widely distributed throughout the genome. These G4s play essential roles in gene transcription and genome stability regulation. Especially, elevated G4 levels in cells deficient in the Bloom syndrome helicase (BLM) significantly enhance HR at G4 sites, potentially threatening genome stability. Here, we investigated the role of G4-binding protein Yin Yang-1 (YY1) in modulating HR at G4 sites in human cells. Our results show that YY1’s binding to G4 structures suppresses sister chromatid exchange after BLM knockdown, and YY1’s chromatin occupancy negatively correlates with the overall HR rate observed across the genome. By limiting RAD51 homolog 1 (RAD51) access, YY1 preferentially binds to essential genomic regions, shielding them from excessive HR. Our findings unveil a novel role of YY1–G4 interaction, revealing novel insights into cellular mechanisms involved in HR regulation.

中文翻译：

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YY1 参与人类细胞鸟嘌呤四联体位点的同源重组抑制


同源重组 (HR) 是修复 DNA 双链断裂和促进遗传多样性的关键过程。然而，HR 在整个基因组中的发生并不均匀，某些基因组特征会影响其活性。其中一个特征是鸟嘌呤四链体 (G4) 的存在，这是一种广泛分布在整个基因组中的稳定二级结构。这些 G4 在基因转录和基因组稳定性调节中发挥着重要作用。特别是，在布鲁姆综合征解旋酶 (BLM) 缺陷的细胞中，G4 水平升高会显着增强 G4 位点的 HR，可能威胁基因组稳定性。在这里，我们研究了 G4 结合蛋白 Yin Yang-1 (YY1) 在调节人类细胞 G4 位点 HR 中的作用。我们的结果表明，YY1 与 G4 结构的结合抑制了 BLM 敲低后的姐妹染色单体交换，并且 YY1 的染色质占用率与在整个基因组中观察到的总体 HR 率呈负相关。通过限制 RAD51 同源物 1 (RAD51) 的访问，YY1 优先结合重要基因组区域，保护它们免受过度 HR 的影响。我们的研究结果揭示了 YY1-G4 相互作用的新作用，揭示了涉及 HR 调节的细胞机制的新见解。