RecQL5, a mammalian RecQ family protein, is involved in the regulation of transcription elongation, DNA damage response, and DNA replication. Here, we identified and characterized an alternative splicing isoform of RECQL5 (RECQL5β1), which contains 17 additional amino acid residues within the RECQL5 KIX domain when compared with the canonical isoform (RECQL5β). RECQL5β1 had a markedly decreased binding affinity to RNA polymerase II (Pol II) and poorly competed with the transcription elongation factor TFIIS for binding to Pol II. As a result, this isoform has a weaker activity for repression of transcription elongation. In contrast, we discovered that RECQL5β1 could bind stronger to MRE11, which is a primary sensor of DNA double-strand breaks (DSBs). Furthermore, we found that RECQL5β1 promoted DNA repair in the RECQL5β1 rescue cells. These results suggest that RECQL5β mainly functions as a transcription repressor, while the newly discovered RECQL5β1 has a specialized role in DNA damage response. Taken together, our data suggest a cellular-functional specialization for each KIX splicing isoform in the cell.

RecQL5 是一种哺乳动物 RecQ 家族蛋白，参与转录延伸、DNA 损伤反应和 DNA 复制的调节。在这里，我们鉴定并表征了 RECQL5 (RECQL5β1) 的替代剪接同种型，与经典同种型 (RECQL5β) 相比，它在 RECQL5 KIX 域内包含 17 个额外的氨基酸残基。RECQL5β1 与 RNA 聚合酶 II (Pol II) 的结合亲和力显着降低，并且与转录延伸因子 TFIIS 竞争与 Pol II 的结合能力较差。因此，这种同工型具有较弱的转录延伸抑制活性。相比之下，我们发现 RECQL5β1 可以与 MRE11 更强地结合，MRE11 是 DNA 双链断裂 (DSB) 的主要传感器。此外，我们发现 RECQL5β1 促进了RECQL5β1 中的DNA 修复拯救细胞。这些结果表明 RECQL5β 主要用作转录抑制因子，而新发现的 RECQL5β1 在 DNA 损伤反应中具有特殊作用。总之，我们的数据表明细胞中每个 KIX 剪接亚型的细胞功能特化。