Human RecQ helicases play diverse roles in the maintenance of genomic stability. Inactivating mutations in 3 of the 5 human RecQ helicases are responsible for the pathogenesis of Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndrome (RTS), RAPADILINO, and Baller-Gerold syndrome (BGS). WS, BS, and RTS patients are at increased risk for developing many age-associated diseases including cancer. Mutations in RecQL1 and RecQL5 have not yet been associated with any human diseases so far. In terms of disease outcome, RecQL4 deserves special attention because mutations in RecQL4 result in 3 autosomal recessive syndromes (RTS type II, RAPADILINO, and BGS). RecQL4, like other human RecQ helicases, has been demonstrated to play a crucial role in the maintenance of genomic stability through participation in diverse DNA metabolic activities. Increased incidence of osteosarcoma in RecQL4-mutated RTS patients and elevated expression of RecQL4 in sporadic cancers including osteosarcoma suggest that loss or gain of RecQL4 expression is linked with cancer susceptibility. In this review, current and future perspectives are discussed on the potential use of RecQL4 as a novel cancer therapeutic target.
Cytogenet Genome Res

中文翻译：

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人类 RecQL4 作为癌症治疗的新分子靶点

人类 RecQ 解旋酶在维持基因组稳定性方面发挥着不同的作用。5 种人类 RecQ 解旋酶中的 3 种失活突变导致 Werner 综合征 (WS)、Bloom 综合征 (BS)、Rothmund-Thomson 综合征 (RTS)、RAPADILINO 和 Baller-Gerold 综合征 (BGS) 的发病机制。WS、BS 和 RTS 患者发生许多与年龄相关的疾病（包括癌症）的风险增加。迄今为止，RecQL1 和 RecQL5 中的突变尚未与任何人类疾病相关联。在疾病结果方面，RecQL4 值得特别关注，因为 RecQL4 的突变导致 3 种常染色体隐性遗传综合征（RTS II 型、RAPADILINO 和 BGS）。与其他人类 RecQ 解旋酶一样，RecQL4 已被证明通过参与不同的 DNA 代谢活动在维持基因组稳定性方面发挥着至关重要的作用。RecQL4 突变的 RTS 患者骨肉瘤的发病率增加，以及包括骨肉瘤在内的散发性癌症中 RecQL4 的表达升高表明 RecQL4 表达的丧失或增加与癌症易感性有关。在这篇综述中，讨论了 RecQL4 作为新型癌症治疗靶点的潜在用途的当前和未来前景。
细胞遗传基因组研究