Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks

Article Article scientifique Article Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks eng 2016-12 author Sotiriou Sotirios 730065 author Kamileri Irene author Lugli Natalia 706163 author Evangelou Konstantinos author Da-Ré Caterina author Huber Florian 716886 author Padayachy Laura 660292 author Tardy Sébastien 784523 Section des sciences pharmaceutiques (FARMA) author Nicati Noémie Lauren 756801 author Barriot Samia 752901 Département de biologie moléculaire et cellulaire (MOCEL) author Ochs Fena author Lukas Claudia author Lukas Jiri author Gorgoulis Vassilis G. author Scapozza Leonardo 0000-0003-1079-648X 600318 Section des sciences pharmaceutiques (FARMA) author Halazonetis Thanos 641033 Département de biologie moléculaire et cellulaire (MOCEL) 1127-1134 10.1016/j.molcel.2016.10.038 27984746 1097-2765 PMC5179496 https://linkinghub.elsevier.com/retrieve/pii/S1097276516307079 Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells. DNA recombination DNA replication stress RAD52 Break-induced replication Cancer Dewey 615 Dewey 570 Swiss National Science Foundation DNA Damage Checkpoint Pathways 160322 CH Projects Novo Nordisk Fonden NNF 14CC0001 Novo Nordisk Foundation Center for Protein Research PI Jiri Lukas General Secretariat for Research and Technology II-3020 European Commission KrÃ¦ftens BekÃ¦mpelse R72-A4436 European Molecular Biology Organization European Research Council CRSI33_130016 43 Département de biologie moléculaire 161 31 Section des sciences pharmaceutiques 17 false 880 Biochimie pharmaceutique Molecular cell 64 6 8900f987-c884-40a7-8aae-bb0c7b08361d Article (Published version) Public HALAZONETIS07.pdf 2101303 application/pdf CC BY-NC-ND-4.0 a26f6cc686bc0492fe7a5a785c00a828d96c5764bf35ab03c38ef76de22be862 openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire Faculté des sciences / Section des sciences pharmaceutiques

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks	Molecular cell			2016	25	10

Archive ouverte UNIGE

Nicati, Noémie Lauren