Myc-driven tumorigenesis involves a non-transcriptional role for Myc in over-activating replicative Cdc45-MCM-GINS (CMG) helicases. Excessive stimulation of CMG helicases by Myc mismanages CMG function by diminishing the number of reserve CMGs necessary for fidelity of DNA replication and recovery from replicative stresses. One potential outcome of these events is the creation of DNA damage that alters genomic structure/function, thereby acting as a driver for tumorigenesis and tumor heterogeneity. Intriguingly, another potential outcome of this Myc-induced CMG helicase over-activation is the creation of a vulnerability in cancer whereby tumor cells specifically lack enough unused reserve CMG helicases to recover from fork-stalling drugs commonly used in chemotherapy. This review provides molecular and clinical support for this provocative hypothesis that excessive activation of CMG helicases by Myc may not only drive tumorigenesis, but also confer an exploitable "reserve CMG helicase vulnerability" that supports developing innovative CMG-focused therapeutic approaches for cancer management.

中文翻译：

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Myc 和复制性 CMG 解旋酶：癌症的产生和破坏：CMG 解旋酶的 Myc 过度激活会驱动肿瘤发生，并在 CMG 中产生治疗干预的脆弱性。

Myc 驱动的肿瘤发生涉及 Myc 在过度激活复制性 Cdc45-MCM-GINS (CMG) 解旋酶中的非转录作用。Myc 对 CMG 解旋酶的过度刺激会减少 DNA 复制保真度和从复制应激中恢复所需的储备 CMG 数量，从而错误地管理 CMG 功能。这些事件的一个潜在结果是产生 DNA 损伤，改变基因组结构/功能，从而成为肿瘤发生和肿瘤异质性的驱动因素。有趣的是，Myc 诱导的 CMG 解旋酶过度激活的另一个潜在结果是在癌症中产生脆弱性，即肿瘤细胞特别缺乏足够的未使用的储备 CMG 解旋酶来从化疗中常用的叉停顿药物中恢复。本综述为这一具有争议性的假设提供了分子和临床支持，即 Myc 对 CMG 解旋酶的过度激活不仅可能驱动肿瘤发生，而且还赋予可利用的“保留 CMG 解旋酶脆弱性”，支持开发以 CMG 为重点的创新癌症治疗方法。