Xu Xiaohua, Liu Yilun
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.
EMBO J. 2009 Mar 4;28(5):568-77. doi: 10.1038/emboj.2009.13. Epub 2009 Jan 29.
Human RECQ helicases have been linked to distinct clinical diseases with increased cancer rates and premature ageing. All RECQ proteins, except RECQ4, have been shown to be functional helicases. Mutations in RECQ4 lead to Rothmund-Thomson syndrome (RTS), and mouse models reveal that the conserved helicase motifs are required for avoidance of RTS. Furthermore, the amino (N) terminus of RECQ4 shares homology with yeast DNA replication initiation factor, Sld2, and is vital for embryonic development. Here, in contrast to previous reports, we show that RECQ4 exhibits DNA helicase activity. Importantly, two distinct regions of the protein, the conserved helicase motifs and the Sld2-like N-terminal domain, each independently promote ATP-dependent DNA unwinding. Taken together, our data provide the first biochemical clues underlying the molecular function of RECQ4 in DNA replication and genome maintenance.
人类RECQ解旋酶与癌症发病率增加和早衰的不同临床疾病有关。除RECQ4外，所有RECQ蛋白均已被证明是具有功能的解旋酶。RECQ4中的突变会导致罗思蒙德-汤姆森综合征（RTS），小鼠模型表明保守的解旋酶基序是避免RTS所必需的。此外，RECQ4的氨基（N）末端与酵母DNA复制起始因子Sld2具有同源性，对胚胎发育至关重要。在这里，与之前的报道相反，我们表明RECQ4具有DNA解旋酶活性。重要的是，该蛋白的两个不同区域，即保守的解旋酶基序和Sld2样N末端结构域，各自独立地促进ATP依赖的DNA解旋。综上所述，我们的数据为RECQ4在DNA复制和基因组维持中的分子功能提供了首个生化线索。
