Maity Jyotirindra, Horibata Sachi, Zurcher Grant, Lee Jung-Min
Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancers (Basel). 2022 Feb 26;14(5):1219. doi: 10.3390/cancers14051219.
RecQ helicases are essential for DNA replication, recombination, DNA damage repair, and other nucleic acid metabolic pathways required for normal cell growth, survival, and genome stability. More recently, RecQ helicases have been shown to be important for replication fork stabilization, one of the major mechanisms of PARP inhibitor resistance. Cancer cells often have upregulated helicases and depend on these enzymes to repair rapid growth-promoted DNA lesions. Several studies are now evaluating the use of RecQ helicases as potential biomarkers of breast and gynecologic cancers. Furthermore, RecQ helicases have attracted interest as possible targets for cancer treatment. In this review, we discuss the characteristics of RecQ helicases and their interacting partners that may be utilized for effective treatment strategies (as cancers depend on helicases for survival). We also discuss how targeting helicase in combination with DNA repair inhibitors (i.e., PARP and ATR inhibitors) can be used as novel approaches for cancer treatment to increase sensitivity to current treatment to prevent rise of treatment resistance.
RecQ解旋酶对于DNA复制、重组、DNA损伤修复以及正常细胞生长、存活和基因组稳定性所需的其他核酸代谢途径至关重要。最近，RecQ解旋酶已被证明对复制叉稳定很重要，这是PARP抑制剂耐药的主要机制之一。癌细胞通常具有上调的解旋酶，并依赖这些酶来修复快速生长促进的DNA损伤。目前有几项研究正在评估将RecQ解旋酶用作乳腺癌和妇科癌症潜在生物标志物的用途。此外，RecQ解旋酶作为癌症治疗的可能靶点已引起关注。在这篇综述中，我们讨论了RecQ解旋酶的特征及其相互作用伙伴，这些可能用于有效的治疗策略（因为癌症依赖解旋酶生存）。我们还讨论了将解旋酶与DNA修复抑制剂（即PARP和ATR抑制剂）联合靶向如何用作癌症治疗的新方法，以提高对当前治疗的敏感性，防止治疗耐药性的上升。
