Human RecQL4 helicase plays critical roles in the maintenance of genomic stability. Mutations in RecQL4 helicase results in three clinically related autosomal recessive disorders: Rothmund–Thomson syndrome (RTS), RAPADILINO, and Baller–Gerold syndrome. In addition to several premature aging features, RTS patients are characterized by aneuploidy involving either loss or gain of a single chromosome. Chromosome mosaicism and isochromosomes involving chromosomes 2, 7, and 8 have been reported in RecQL4-deficient RTS patients, but the precise role of RecQL4 in chromosome segregation/stability remains to be elucidated. Here, we demonstrate that RecQL4 physically and functionally interacts with Aurora B kinase (AURKB) and stabilizes its expression by inhibiting its ubiquitination process. Our study indicates that the N-terminus of RecQL4 interacts with the catalytic domain of AURKB. Strikingly, RecQL4 suppression reduces the expression of AURKB leading to mitotic irregularities and apoptotic cell death. RecQL4 suppression increases the proportion of cells at the G2/M phase followed by an extensive cell death, presumably owing to the accumulation of mitotic irregularities. Both these defects (accumulation of cells at G2/M phase and an improper mitotic exit to sub-G1) are complemented by the ectopic expression of AURKB. Finally, evidence is provided for the requirement of both human telomerase reverse transcriptase and RecQL4 for stable immortalization and longevity of RTS fibroblasts. Collectively, our study suggests that the RecQL4–AURKB axis is essential for cellular proliferation, cell cycle progression, and mitotic stability in human cells.

人RecQL4解旋酶在维持基因组稳定性中起关键作用。RecQL4解旋酶中的突变导致三种临床相关的常染色体隐性遗传疾病：Rothmund-Thomson综合征（RTS），RAPADILINO和Baller-Gerold综合征。除了一些过早的衰老特征外，RTS患者的特征还在于非整倍性，涉及丢失或增加单个染色体。在RecQL4缺陷型RTS患者中已经报道了涉及2、7和8号染色体的染色体镶嵌和同染色体，但是RecQL4在染色体分离/稳定性中的确切作用仍有待阐明。在这里，我们证明RecQL4在物理和功能上与Aurora B激酶（AURKB）相互作用，并通过抑制其泛素化过程来稳定其表达。我们的研究表明，RecQL4的N末端与AURKB的催化域相互作用。令人惊讶的是，RecQL4抑制作用会降低AURKB的表达，从而导致有丝分裂异常和凋亡性细胞死亡。RecQL4抑制会增加G2 / M期细胞的比例，随后导致大量细胞死亡，这可能是由于有丝分裂异常的积累所致。这些缺陷（G2 / M期的细胞蓄积和亚G1的不正确的有丝分裂出口）都被AURKB的异位表达所弥补。最后，提供了证据表明人类端粒酶逆转录酶和RecQL4都需要RTS成纤维细胞稳定永生和长寿。总体而言，我们的研究表明RecQL4–AURKB轴对于细胞增殖，细胞周期进程，