ALT控制,删除:FANCM作为端粒选择性延长的抗癌靶点。

Julienne J O'Rourke, Rohan Bythell-Douglas, Elyse A Dunn, Andrew J Deans
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引用次数: 13

摘要

断裂诱导复制是一种特殊类型的DNA修复,在端粒酶阴性的癌细胞端粒延伸中具有增选作用。这种端粒的选择性延长(ALT)在大约10%的癌症中是生存所必需的,但在软组织来源的肉瘤中高达50%。在最近的几项研究中,我们和其他人证明了FANCM(一种DNA转位酶蛋白)的表达和活性对alt相关癌症的生存至关重要。在这里,我们总结了FANCM耗尽如何以及为什么导致alt控制的癌症缺失,主要是通过断裂诱导复制的过度激活。我们还讨论了FANCM如何能够和已经靶向癌细胞杀伤,包括ALT和其他遗传背景的潜在机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

ALT control, delete: FANCM as an anti-cancer target in Alternative Lengthening of Telomeres.

ALT control, delete: FANCM as an anti-cancer target in Alternative Lengthening of Telomeres.

ALT control, delete: FANCM as an anti-cancer target in Alternative Lengthening of Telomeres.

ALT control, delete: FANCM as an anti-cancer target in Alternative Lengthening of Telomeres.

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.

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