The RECQL helicase prevents replication fork collapse during replication stress

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 d...

Full description

Saved in:
Bibliographic Details
Published inLife science alliance Vol. 3; no. 10; p. e202000668
Main Authors Benedict, Bente, van Bueren, Marit AE, van Gemert, Frank PA, Lieftink, Cor, Guerrero Llobet, Sergi, van Vugt, Marcel ATM, Beijersbergen, Roderick L, te Riele, Hein
Format Journal Article
LanguageEnglish
Published Life Science Alliance LLC 01.10.2020
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:Marit AE van Bueren and Frank PA van Gemert contributed equally to this work
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.202000668