RT Journal Article
SR Electronic
T1 The RECQL helicase prevents replication fork collapse during replication stress
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000668
DO 10.26508/lsa.202000668
VO 3
IS 10
A1 Benedict, Bente
A1 van Bueren, Marit AE
A1 van Gemert, Frank PA
A1 Lieftink, Cor
A1 Guerrero Llobet, Sergi
A1 van Vugt, Marcel ATM
A1 Beijersbergen, Roderick L
A1 te Riele, Hein
YR 2020
UL https://www.life-science-alliance.org/content/3/10/e202000668.abstract
AB 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.