TY - JOUR T1 - The RECQL helicase prevents replication fork collapse during replication stress JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000668 VL - 3 IS - 10 SP - e202000668 AU - Bente Benedict AU - Marit AE van Bueren AU - Frank PA van Gemert AU - Cor Lieftink AU - Sergi Guerrero Llobet AU - Marcel ATM van Vugt AU - Roderick L Beijersbergen AU - Hein te Riele Y1 - 2020/10/01 UR - https://www.life-science-alliance.org/content/3/10/e202000668.abstract N2 - Most tumors lack the G1/S phase checkpoint and are insensitive to antigrowth signals. Loss of G1/S control can severely perturb DNA replication as revealed by slow replication fork progression and frequent replication fork stalling. Cancer cells may thus rely on specific pathways that mitigate the deleterious consequences of replication stress. To identify vulnerabilities of cells suffering from replication stress, we performed an shRNA-based genetic screen. We report that the RECQL helicase is specifically essential in replication stress conditions and protects stalled replication forks against MRE11-dependent double strand break (DSB) formation. In line with these findings, knockdown of RECQL in different cancer cells increased the level of DNA DSBs. Thus, RECQL plays a critical role in sustaining DNA synthesis under conditions of replication stress and as such may represent a target for cancer therapy. ER -