ALT control, delete: FANCM as an anti-cancer target in Alternative Lengthening of Telomeres. (1st January 2019)

• Record Type: Journal Article
• Authors: O'Rourke, Julienne J; Bythell-Douglas, Rohan; Dunn, Elyse A; Deans, Andrew J
• Is Part Of: Nucleus. Volume 10:Number 1(2019)
• Page Start: 221
• Page End: 230
• Publication Date: 2019-01-01
• Subjects: Telomeres -- DNA repair -- Fanconi anemia -- chemotherapy -- break-induced replication -- precision medicine -- synthetic lethal; Cell nuclei -- Periodicals; Biology -- Periodicals; Biology; Cell nuclei; Periodicals; 571.6605
• DOI: 10.1080/19491034.2019.1685246
• Languages: English
• ISSNs: 1949-1034

Abstract

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.