@article{b639390f3a8445af8a5578d70121fe85,
title = "PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells",
abstract = "Reversed replication forks are degraded in BRCA-deficient cells. Quinet et al. show that treatment with multiple cisplatin doses promotes PRIMPOL repriming while suppressing fork reversal and preventing degradation. These studies identify a new function of PRIMPOL in the replication stress response and explain how cells adapt to multiple drug doses.",
keywords = "ATR, BRCA, DNA damage, DNA replication, PRIMPOL, adaptive response, replication fork repriming, replication fork reversal, replication stress response, ssDNA gaps",
author = "Annabel Quinet and Stephanie Tirman and Jessica Jackson and Sa{\v s}a {\v S}vikovi{\'c} and Delphine Lema{\c c}on and Denisse Carvajal-Maldonado and Daniel Gonz{\'a}lez-Acosta and Vessoni, \{Alexandre T.\} and Emily Cybulla and Matthew Wood and Steven Tavis and Batista, \{Luis F.Z.\} and Juan M{\'e}ndez and Sale, \{Julian E.\} and Alessandro Vindigni",
note = "Funding Information: We would like to thank Shunichi Takeda (Kyoto University) for providing DT40 smarcal1 mutant and targeting constructs and Aidan Doherty (University of Sussex) for providing the primpol DT40 targeting constructs. We thank the Research Microscopy Core Facility and the Flow Cytometry Research Core Facility of Saint Louis University for technical support. We thank the Genome Engineering and iPSC Center (GEiC) at Washington University in St. Louis for gRNA validation services and generation of the PRIMPOL KO U2OS cells. The work in the A.V. laboratory is supported by NIH grants R01CA237263 and R01GM108648 , by DOD BRCP Breakthrough Award BC151728 , and by the Siteman Cancer Center at Washington University in St. Louis. Work in the J.E.S. laboratory is supported by the UK Medical Research Council through a central grant to the Laboratory of Molecular Biology ( U105178808 ). The work in J.M. laboratory is supported by the Spanish Ministry of Science, Innovation, and Universities (grant BFU2016-80402-R , co-financed with European Union ERDF funds). Work in the L.B laboratory is supported by NIH grant R01HL137793 and the Siteman Cancer Center at Washington University in St. Louis. Funding Information: We would like to thank Shunichi Takeda (Kyoto University) for providing DT40 smarcal1 mutant and targeting constructs and Aidan Doherty (University of Sussex) for providing the primpol DT40 targeting constructs. We thank the Research Microscopy Core Facility and the Flow Cytometry Research Core Facility of Saint Louis University for technical support. We thank the Genome Engineering and iPSC Center (GEiC) at Washington University in St. Louis for gRNA validation services and generation of the PRIMPOL KO U2OS cells. The work in the A.V. laboratory is supported by NIH grants R01CA237263 and R01GM108648, by DOD BRCP Breakthrough Award BC151728, and by the Siteman Cancer Center at Washington University in St. Louis. Work in the J.E.S. laboratory is supported by the UK Medical Research Council through a central grant to the Laboratory of Molecular Biology (U105178808). The work in J.M. laboratory is supported by the Spanish Ministry of Science, Innovation, and Universities (grant BFU2016-80402-R, co-financed with European Union ERDF funds). Work in the L.B laboratory is supported by NIH grant R01HL137793 and the Siteman Cancer Center at Washington University in St. Louis. A.Q. designed the project and performed most of the experiments with the assistance of S.T. D.C.M. E.C. and M.W.; J.J. performed the EM experiments with the assistance of A.Q. and D.L.; S.S. performed the experiments with the DT40 cells; D.G.-A. performed the chromatin fractionation experiments; S.T. contributed to the analysis of the colony-forming assays; A.T.V. established the stable UW+PRIMPOL cell line. L.B. J.M. and J.E.S. assisted with experimental design and manuscript finalization; A.V. designed and supervised the project and wrote the manuscript with the assistance of A.Q. The authors decleare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2020",
month = feb,
day = "6",
doi = "10.1016/j.molcel.2019.10.008",
language = "English",
volume = "77",
pages = "461--474.e9",
journal = "Molecular cell",
issn = "1097-2765",
number = "3",
}