@article{765d5011a7dc42e1893ed32e4ee21196,
title = "CARM1 regulates replication fork speed and stress response by stimulating PARP1",
abstract = "DNA replication forks use multiple mechanisms to deal with replication stress, but how the choice of mechanisms is made is still poorly understood. Here, we show that CARM1 associates with replication forks and reduces fork speed independently of its methyltransferase activity. The speeding of replication forks in CARM1-deficient cells requires RECQ1, which resolves reversed forks, and RAD18, which promotes translesion synthesis. Loss of CARM1 reduces fork reversal and increases single-stranded DNA (ssDNA) gaps but allows cells to tolerate higher replication stress. Mechanistically, CARM1 interacts with PARP1 and promotes PARylation at replication forks. In vitro, CARM1 stimulates PARP1 activity by enhancing its DNA binding and acts jointly with HPF1 to activate PARP1. Thus, by stimulating PARP1, CARM1 slows replication forks and promotes the use of fork reversal in the stress response, revealing that CARM1 and PARP1 function as a regulatory module at forks to control fork speed and the choice of stress response mechanisms.",
keywords = "CARM1, PARP1, PARylation, PrimPol, RECQ1, fork reversal, fork speed, replication fork, replication stress, translesion synthesis",
author = "Genois, {Marie Michelle} and Gagn{\'e}, {Jean Philippe} and Takaaki Yasuhara and Jessica Jackson and Sneha Saxena and Langelier, {Marie France} and Ivan Ahel and Bedford, {Mark T.} and Pascal, {John M.} and Alessandro Vindigni and Poirier, {Guy G.} and Lee Zou",
note = "Funding Information: We thank Dr. Juan Mendez for the PrimPol antibody; Dr. Shyamala Maheswaran for MCF10A cells; and members of the Zou, Dyson, Lan, and Elia labs for discussions. M.-M.G. was partially supported by a postdoctoral fellowship from Fonds de recherche Sant{\'e} Qu{\'e}bec (FRQS). L.Z. is the James & Patricia Poitras Endowed Chair in Cancer Research and was supported by a Jim & Ann Orr Massachusetts General Hospital Research Scholar Award. This work is supported by grants from the NIH, United States (GM126421 to M.T.B. CA237263 to A.V. CA248526 to A.V. and L.Z. and CA218856 and CA197779 to L.Z.). M.-M.G. and L.Z. designed the project. M.-M.G. J.-P.G. T.Y. J.J. and S.S. performed the experiments and data analysis. A.V. G.G.P. and L.Z. supervised the experiments and data analysis. M.F.L. I.A. M.T.B. and J.M.P. provided critical reagents and contributed intellectually. M.-M.G. and L.Z. wrote the manuscript with help from all other authors. L.Z. is a member of the advisory board of Molecular Cell. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = feb,
day = "18",
doi = "10.1016/j.molcel.2020.12.010",
language = "English",
volume = "81",
pages = "784--800.e8",
journal = "Molecular Cell",
issn = "1097-2765",
number = "4",
}