ABSTRACT Break-induced replication is a specific type of DNA repair that has a co-opted role in telomere extension by telomerase-negative cancer cells. This Alternative Lengthening of Telomeres (or ‘ALT’) is required for viability in approximately 10% of all carcinomas, but up to 50% of the soft-tissue derived sarcomas. In several recent studies, we and others demonstrate that expression and activity of FANCM, a DNA translocase protein, is essential for the viability of ALT-associated cancers. Here we provide a summary of how and why FANCM depletion leads to deletion of ALT-controlled cancers, predominantly through a hyper-activation of break-induced replication. We also discuss how FANCM can and has been targeted in cancer cell killing, including potential opportunities in ALT and other genetic backgrounds.

中文翻译：

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ALT 控制，删除：FANCM 作为端粒替代延长中的抗癌靶点

摘要 断裂诱导的复制是一种特定类型的 DNA 修复，在端粒酶阴性癌细胞的端粒延伸中具有共同作用。大约 10% 的所有癌，但多达 50% 的软组织来源的肉瘤的生存能力需要这种端粒的替代延长（或“ALT”）。在最近的几项研究中，我们和其他人证明 FANCM（一种 DNA 转位酶蛋白）的表达和活性对于 ALT 相关癌症的生存能力至关重要。在这里，我们总结了 FANCM 消耗如何以及为什么导致 ALT 控制的癌症的缺失，主要是通过断裂诱导复制的过度激活。我们还讨论了 FANCM 如何能够并且已经成为癌细胞杀伤的目标，包括 ALT 和其他遗传背景中的潜在机会。