Thakkar Megha K, Lee Jamie, Meyer Stefan, Chang Vivian Y
Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA, United States.
Division of Cancer Studies, University of Manchester, Manchester, United Kingdom.
Front Mol Biosci. 2022 Jun 15;9:887758. doi: 10.3389/fmolb.2022.887758. eCollection 2022.
Named the "caretakers" of the genome, RecQ helicases function in several pathways to maintain genomic stability and repair DNA. This highly conserved family of enzymes consist of five different proteins in humans: RECQL1, BLM, WRN, RECQL4, and RECQL5. Biallelic germline mutations in , , and have been linked to rare cancer-predisposing syndromes. Emerging research has also implicated somatic alterations in RecQ helicases in a variety of cancers, including hematological malignancies, breast cancer, osteosarcoma, amongst others. These alterations in RecQ helicases, particularly overexpression, may lead to increased resistance of cancer cells to conventional chemotherapy. Downregulation of these proteins may allow for increased sensitivity to chemotherapy, and, therefore, may be important therapeutic targets. Here we provide a comprehensive review of our current understanding of the role of RecQ DNA helicases in cancer and discuss the potential therapeutic opportunities in targeting these helicases.
RecQ解旋酶被称为基因组的“守护者”，在多种途径中发挥作用以维持基因组稳定性并修复DNA。这个高度保守的酶家族在人类中由五种不同的蛋白质组成：RECQL1、BLM、WRN、RECQL4和RECQL5。 、 和 的双等位基因种系突变与罕见的癌症易感综合征有关。新兴研究还表明，RecQ解旋酶的体细胞改变与多种癌症有关，包括血液系统恶性肿瘤、乳腺癌、骨肉瘤等。RecQ解旋酶的这些改变，尤其是过表达，可能导致癌细胞对传统化疗的耐药性增加。下调这些蛋白质可能会增加对化疗的敏感性，因此可能是重要的治疗靶点。在此，我们全面综述了目前对RecQ DNA解旋酶在癌症中的作用的理解，并讨论了靶向这些解旋酶的潜在治疗机会。
